🎯 Drug Targets

Browse 185 drug targets with druggability analysis, composite scores, and clinical context

185

Targets

10

High Druggability

0.51

Avg Score

15

Target Classes

Druggability Distribution

High: 10Medium: 56Low: 97Unknown: 0

Avg druggability score: 0.423

Clinical Pipeline

Approved: 66Phase III: 23Phase II: 50Phase I: 26Preclinical: 20

Total compounds: 405 · Approved: 110

GABRA1 Gamma-aminobutyric acid receptor subunit alpha-1 Approved

Ion Channel High Druggability

GABRA1 mediates inhibitory neurotransmission through GABA-A receptor subunit composition, modulating neuronal excitability and synaptic signaling. In neurodegeneration contexts, alterations in GABRA1 expression or function can contribute to neuronal hyperexcitability, oxidative stress, and potentially accelerated cellular damage mechanisms associated with progressive neurological disorders.

LDLR Low density lipoprotein receptor Approved

Receptor High Druggability

Upregulation through PCSK9 inhibition or direct receptor modulation

CACNA1G Voltage-dependent T-type calcium channel subunit a Approved

Ion Channel High Druggability

Small molecule blocker of T-type calcium channel activity

DRD2 Dopamine receptor D2 Approved

Gpcr High Druggability

Small molecule agonist or antagonist modulating dopamine signaling

IDH2 Isocitrate Dehydrogenase 2 Approved

Enzyme High Druggability

Small molecule inhibitor of mutant IDH2 enzyme activity

P2RX7 P2X purinoreceptor 7 Phase II

Ion Channel High Druggability

Selective P2X7 receptor antagonists blocking ATP-gated ion channel

BCL2L1 BCL2 Like 1 Approved

Signaling Protein High Druggability

Small molecule inhibitor of anti-apoptotic protein function

MTNR1A Melatonin receptor 1A Approved

Gpcr Medium Druggability

Small molecule agonists that activate G-protein coupled receptor signaling

RAB7A Ras-related protein Rab-7a Phase III

Signaling Protein High Druggability

RAB7A inhibitors or modulators would block or enhance GTPase-mediated late endosome and lysosome trafficking, disrupting autophagy flux and lysosomal degradation pathways. This can either impair pathogenic protein clearance (in certain cancers) or restore lysosomal function (in storage disorders and neurodegeneration).

PRKAA1 AMP-activated protein kinase catalytic subunit alp Approved

Kinase Medium Druggability

Small molecule activator of AMP-activated protein kinase

KCNK2 Potassium two pore domain channel subfamily K memb Approved

Ion Channel Medium Druggability

KCNK2 encodes a two-pore domain potassium channel (TREK-1) that regulates neuronal excitability, membrane potential, and cellular responsiveness to mechanical and chemical stimuli in the central nervous system. In neurodegeneration, TREK-1 modulation can influence neuronal survival, mitochondrial function, and potentially mitigate oxidative stress and excitotoxicity through precise potassium conductance regulation.

C3 Complement C3 Approved

Signaling Protein Medium Druggability

Small molecule inhibitor of complement activation or convertase activity

PARP1 Poly [ADP-ribose] polymerase 1 Approved

Enzyme Medium Druggability

Competitive inhibitors of PARP1 enzymatic activity blocking DNA repair

TH Tyrosine hydroxylase Approved

Enzyme Medium Druggability

Enzyme replacement therapy via L-DOPA supplementation to bypass reduced TH activity

P2RY1 P2Y purinoreceptor 1 Phase I

Gpcr Low Druggability

GPCR antagonists or agonists modulating purinergic signaling

IL1B Interleukin-1 beta Approved

Ligand Medium Druggability

IL-1 receptor antagonist or neutralizing monoclonal antibody

MTNR1B Melatonin receptor 1B Approved

Gpcr High Druggability

Small molecule agonists that activate G-protein coupled receptor signaling

NLRP3 NACHT, LRR and PYD domains-containing protein 3 Approved

Signaling Protein Medium Druggability

Small molecule inhibitors targeting NLRP3 inflammasome assembly or activation

G3BP1 Ras GTPase-activating protein-binding protein 1 Phase II

Signaling Protein Medium Druggability

G3BP1 inhibitors would prevent stress granule assembly and stabilization by disrupting the interaction between G3BP1 and its binding partners, potentially reducing pathological aggregation of TDP-43 and FUS proteins. This mechanism could alleviate neurodegeneration in conditions characterized by aberrant stress granule formation and RNA metabolism dysfunction.

GLP1R Glucagon-like peptide-1 receptor Approved

Gpcr Medium Druggability

GLP-1 receptor agonist peptides and small molecule modulators

HSP90AA1 Heat Shock Protein 90 Alpha Family Class A Member Phase III

Chaperone Low Druggability

Small molecule inhibitor binding to ATP-binding pocket of chaperone

PDGFRB Platelet-derived growth factor receptor beta Approved

Kinase Medium Druggability

Small molecule inhibitor of receptor tyrosine kinase activity

TREM2 Triggering receptor expressed on myeloid cells 2 Phase II

Receptor Low Druggability

Agonist antibodies that enhance TREM2 signaling to promote microglial function

CGAS Cyclic GMP-AMP synthase Phase III

Enzyme Medium Druggability

Small molecule inhibitor of cyclic dinucleotide synthesis

APOE Apolipoprotein E Phase II

Ligand Medium Druggability

Protein-protein interaction modulator or lipid metabolism enhancer

ADORA2A Adenosine A2A receptor Approved

Gpcr Medium Druggability

Small molecule antagonists blocking adenosine A2A receptor signaling

SLC7A11 Cystine/glutamate transporter Approved

Transporter Medium Druggability

Small molecule inhibition of cystine/glutamate exchange

HSPA1A Heat Shock Protein Family A Member 1A Phase III

Chaperone Medium Druggability

Small molecule activators or allosteric modulators of chaperone function

ADRA2A Alpha-2A adrenergic receptor Approved

Gpcr Medium Druggability

Small molecule agonists and antagonists modulating noradrenergic signaling

ULK1 Unc-51 like autophagy activating kinase 1 Phase I

Kinase Low Druggability

Small molecule activators or inhibitors of ULK1 kinase activity to modulate autophagy

SNCA Synuclein alpha Phase II

Structural Protein Medium Druggability

Immunotherapy targeting alpha-synuclein aggregates or small molecules preventing aggregation

HCRTR1 Hypocretin Receptor 1 Approved

Gpcr Medium Druggability

Small molecule antagonist blocking orexin receptor signaling

FCGRT Fc fragment of IgG receptor and transporter Approved

Transporter Medium Druggability

Monoclonal antibody blocking FcRn-mediated IgG recycling

HCRTR2 Hypocretin Receptor 2 Approved

Gpcr Medium Druggability

Small molecule antagonist blocking orexin receptor signaling

P2RY12 P2Y purinoreceptor 12 Approved

Gpcr Medium Druggability

P2Y12 receptor antagonists blocking ADP-mediated signaling

LOX Lysyl oxidase Phase II

Enzyme Low Druggability

Small molecule inhibition of lysyl oxidase enzymatic activity

CX3CR1 C-X3-C Motif Chemokine Receptor 1 Phase II

Gpcr Low Druggability

GPCR antagonist modulating microglial activation and neuroinflammation

SIRT6 Sirtuin-6 Phase I

Epigenetic Regulator Low Druggability

Small molecule activation or inhibition of NAD+-dependent deacetylase activity

TGM2 Protein-glutamine gamma-glutamyltransferase 2 Phase II

Enzyme Medium Druggability

Small molecule inhibitors of transglutaminase enzymatic activity

TFR1 Transferrin receptor protein 1 Approved

Receptor Low Druggability

Monoclonal antibodies targeting receptor or iron chelation affecting iron uptake

CD38 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Approved

Enzyme Medium Druggability

Monoclonal antibody targeting or small molecule inhibitor of NAD+ consuming activity

C1Q Complement C1q Approved

Signaling Protein Low Druggability

Complement cascade inhibitor or antibody-mediated neutralization

BDNF Brain Derived Neurotrophic Factor Phase II

Ligand Low Druggability

Protein replacement therapy or small molecule mimetic

FKBP5 FKBP prolyl isomerase 5 Phase I

Enzyme Medium Druggability

Small molecule inhibitor of prolyl isomerase activity and HSP90 co-chaperone function

MMP9 Matrix metalloproteinase-9 Phase III

Protease Medium Druggability

Small molecule zinc-chelating inhibitors or antibody-based inhibition

NR3C1 Glucocorticoid receptor Approved

Transcription Factor Medium Druggability

Selective glucocorticoid receptor modulators (SRMs) or antagonists

TET2 Tet methylcytosine dioxygenase 2 Phase II

Epigenetic Regulator Low Druggability

Small molecule enhancers of TET2 enzymatic activity or cofactor supplementation

TUBB3 Tubulin beta-3 chain Approved

Structural Protein Medium Druggability

Small molecule stabilizers of microtubule structure or assembly

STX17 Syntaxin-17 Phase II

Structural Protein Medium Druggability

STX17-targeting drugs would enhance or modulate autophagosome-lysosome fusion by facilitating SNARE complex assembly, thereby improving autophagic clearance of misfolded proteins and damaged organelles. This mechanism is particularly relevant for neurodegenerative diseases characterized by protein aggregation.

TLR4 Toll-like receptor 4 Phase III

Receptor Low Druggability

Small molecule antagonist or antibody blocking TLR4-mediated neuroinflammatory signaling

TFRC Transferrin receptor protein 1 Approved

Receptor Medium Druggability

Monoclonal antibodies targeting receptor or iron chelation affecting iron uptake

FOXO1 Forkhead box protein O1 Phase I

Transcription Factor Medium Druggability

Small molecule modulation of protein-DNA interactions or cofactor binding

GJA1 Gap junction alpha-1 protein (Connexin 43) Phase II

Ion Channel Low Druggability

Small molecule modulator of gap junction channel activity

TNFA Tumor necrosis factor alpha Approved

Signaling Protein Medium Druggability

Monoclonal antibodies or soluble receptors that neutralize TNF-alpha activity

TFAM Transcription factor A, mitochondrial Approved

Transcription Factor Medium Druggability

Drugs targeting TFAM would enhance or modulate its transcriptional activity to increase mitochondrial DNA replication and gene expression, thereby boosting mitochondrial biogenesis and ATP production. Alternatively, indirect approaches activate upstream regulators like PGC-1α and SIRT1 to increase TFAM expression and activity.

MIRO1 Mitochondrial Rho GTPase 1 Phase II

Signaling Protein Low Druggability

MIRO1-targeting drugs modulate GTPase activity to enhance mitochondrial transport along axons and improve mitochondrial quality control through selective autophagy. By regulating MIRO1's interaction with kinesin motor proteins and PINK1-mediated mitophagy, these compounds restore energy homeostasis and reduce neuronal stress in neurodegenerative diseases.

SOAT1 Sterol O-acyltransferase 1 Phase III

Enzyme Low Druggability

Small molecule inhibitor of acyl-CoA:cholesterol acyltransferase activity

PRMT1 Protein arginine methyltransferase 1 Phase I

Epigenetic Regulator Low Druggability

Small molecule inhibitor of protein arginine methyltransferase activity

HCN1 Hyperpolarization-activated cyclic nucleotide-gate Approved

Ion Channel Medium Druggability

HCN1 encodes a hyperpolarization-activated cyclic nucleotide-gated channel critical for neuronal pacemaking and synaptic integration, with dysregulation linked to hyperexcitability disorders and potential neurodegeneration mechanisms. Specifically, HCN1 channel dysfunction can alter neuronal excitability, synaptic plasticity, and potentially contribute to neuronal death or dysfunction in conditions like epilepsy and neurodegenerative diseases.

MMP2 Matrix metalloproteinase-2 Phase III

Protease Medium Druggability

Small molecule zinc-chelating inhibitors of metalloprotease activity

CASP1 Caspase-1 Phase II

Protease Medium Druggability

Small molecule covalent inhibitor of caspase-1 proteolytic activity

PPARGC1A Peroxisome proliferator-activated receptor gamma c Approved

Transcription Factor Low Druggability

Small molecule modulator of transcriptional coactivator function

STING1 Stimulator of interferon genes protein 1 Phase II

Signaling Protein Low Druggability

Small molecule agonists or antagonists of cGAS-STING pathway activation

BACE1 Beta-secretase 1 Phase III

Protease Medium Druggability

Small molecule inhibitor of aspartyl protease activity

DNMT1 DNA methyltransferase 1 Approved

Epigenetic Regulator Medium Druggability

Small molecule inhibitor of DNA methyltransferase activity

GPR37 G-protein coupled receptor 37 Approved

Gpcr Low Druggability

GPR37 agonists or modulators would activate the receptor to promote dopaminergic neuron survival and neuroprotection, counteracting the neurodegeneration characteristic of Parkinson's disease. Ligands binding to GPR37 would enhance G-protein signaling cascades that support neuronal viability and function.

GPX4 Glutathione peroxidase 4 Phase II

Enzyme Low Druggability

Small molecule inhibitor or activator of peroxidase activity

ALOX5 5-lipoxygenase Approved

Enzyme Medium Druggability

Small molecule inhibitors blocking leukotriene synthesis

EPHB4 Ephrin type-B receptor 4 Approved

Kinase Low Druggability

Small molecule inhibitor of receptor tyrosine kinase activity

SRPK1 SRSF protein kinase 1 Phase II

Kinase Low Druggability

SRPK1 inhibitors block phosphorylation of serine/arginine-rich splicing factors, modulating alternative splicing patterns implicated in neurodegeneration and cancer. By preventing aberrant splicing, these inhibitors can restore normal protein isoform expression and reduce pathogenic tau accumulation.

HDAC3 Histone Deacetylase 3 Approved

Epigenetic Regulator Low Druggability

Small molecule inhibitor of histone deacetylase enzymatic activity

ANGPT1 Angiopoietin-1 Approved

Ligand Low Druggability

Protein therapeutics or small molecule mimetics activating Tie2 signaling

ABCA1 ATP-binding cassette transporter A1 Approved

Transporter Medium Druggability

Small molecule modulators to enhance cholesterol efflux and HDL formation

FOXO3 Forkhead box protein O3 Approved

Transcription Factor Low Druggability

FOXO3-targeting drugs modulate the PI3K/Akt/FOXO3 signaling pathway to promote FOXO3 nuclear translocation and transcriptional activity, enhancing autophagy, stress resistance, and apoptosis in cancer cells. Indirect activators increase FOXO3 expression or prevent its degradation, thereby amplifying cellular protective responses.

ANXA1 Annexin A1 Approved

Signaling Protein Low Druggability

Calcium-dependent phospholipid binding protein modulator

TGFB1 Transforming growth factor beta-1 Phase III

Ligand Low Druggability

Monoclonal antibodies neutralizing TGF-β1 or small molecule inhibitors of TGF-β signaling

AQP1 Aquaporin-1 Approved

Ion Channel Low Druggability

AQP1 functions as a water channel protein facilitating transmembrane water flux, with emerging evidence suggesting its involvement in neuroinflammatory processes and potential contribution to neuronal cell volume regulation and edema formation in neurodegenerative conditions. In the context of neurodegeneration, AQP1 may modulate neuronal and glial cell responses to oxidative stress, inflammation, and cellular metabolic perturbations, making it a potential strategic target for therapeutic intervention.

LRP1 LDL receptor related protein 1 Phase III

Receptor Low Druggability

Modulation of receptor-mediated endocytosis and clearance pathways

HK2 Hexokinase 2 Phase III

Enzyme Low Druggability

Small molecule inhibitor of glucose phosphorylation

MCOLN1 Mucolipin-1 Phase I

Ion Channel Low Druggability

Small molecule agonists or modulators of lysosomal calcium channel activity

RAB27A Ras-related protein Rab-27A Phase II

Signaling Protein Low Druggability

RAB27A inhibitors would block GTP binding or GTPase activity, preventing the recruitment of effector proteins required for vesicular trafficking and exosome biogenesis. This would reduce the release of extracellular vesicles and potentially modulate intercellular communication in disease states involving excessive exosome-mediated signaling or pathological cargo transfer.

SDC1 Syndecan-1 Phase II

Receptor Low Druggability

Small molecule modulation of heparan sulfate interactions or shedding

CMKLR1 Chemokine-like Receptor 1 Phase II

Gpcr Low Druggability

GPCR antagonist or agonist modulating chemerin signaling

CLOCK Circadian Locomotor Output Cycles Kaput Approved

Transcription Factor Low Druggability

Modulation of circadian transcriptional activity through protein-protein interaction disruption

ALOX15 15-lipoxygenase Approved

Enzyme Low Druggability

Small molecule inhibitors targeting the active site iron and substrate binding

C1QA Complement C1q A Chain Phase II

Signaling Protein Low Druggability

Complement cascade inhibitor or antibody-mediated neutralization

CRH Corticotropin Releasing Hormone Approved

Ligand Low Druggability

CRH receptor antagonist blocking stress hormone signaling

NAMPT Nicotinamide phosphoribosyltransferase Phase II

Enzyme Low Druggability

Small molecule competitive inhibitors of NAD+ biosynthesis enzyme

VCP Valosin containing protein Phase I

Enzyme Medium Druggability

Small molecule inhibitors of VCP ATPase activity affecting protein quality control

BMAL1 Basic Helix-Loop-Helix ARNT Like 1 Phase I

Transcription Factor Low Druggability

Small molecule modulator of circadian transcription

AHR Aryl hydrocarbon receptor Phase II

Transcription Factor Low Druggability

Small molecule modulators affecting ligand-dependent transcriptional activity

LAMP1 Lysosomal associated membrane protein 1 Phase I

Structural Protein Low Druggability

Direct LAMP1 modulators enhance lysosomal membrane trafficking and autophagy flux, while indirect pathway drugs alter lysosomal pH and autophagosome-lysosome fusion dynamics to modulate LAMP1-mediated cellular clearance mechanisms.

ALOX12 12-lipoxygenase Phase I

Enzyme Low Druggability

Small molecule inhibitors of lipoxygenase enzymatic activity

HNRNPA2B1 Heterogeneous Nuclear Ribonucleoprotein A2/B1 Phase II

Other Low Druggability

Therapeutic agents targeting HNRNPA2B1 would work by modulating its RNA-binding activity, preventing pathological protein aggregation, or reducing the formation of cytoplasmic inclusions associated with neurodegeneration. These drugs could utilize antisense oligonucleotides to reduce HNRNPA2B1 expression or small molecules to inhibit its protein-protein interactions and RNA-binding functions.

HCRT Hypocretin/Orexin Approved

Ligand Medium Druggability

Peptide hormone replacement or stabilization approaches

NTN1 Netrin-1 Phase I

Ligand Low Druggability

Modulation of axon guidance and neuronal survival pathways

IL10 Interleukin-10 Phase II

Ligand Low Druggability

Recombinant protein replacement or monoclonal antibody modulation

DNASE2 Deoxyribonuclease 2 lysosomal Phase I

Enzyme Low Druggability

Small molecule inhibitor or activator of nuclease activity

P2RY1ANDP2RX7 P2RY1ANDP2RX7

Receptor High Druggability

Prioritized from 1 SciDEX hypotheses, including: Purinergic Signaling Polarization Control

SST Somatostatin Approved

Ligand Low Druggability

Somatostatin is a peptide neurotransmitter that modulates neuronal signaling by inhibiting hormone release and neuronal excitability, with emerging evidence suggesting its potential neuroprotective role in neurodegenerative processes through regulation of inflammatory responses and synaptic plasticity. In neurodegeneration contexts, SST receptors may serve as modulators of neuroinflammatory cascades and potentially mitigate progressive neuronal damage through receptor-mediated signaling mechanisms.

DNAJB1 DnaJ heat shock protein family (Hsp40) member B1 Phase I

Chaperone Low Druggability

Allosteric modulation of protein-protein interactions with Hsp70

IGF2R Insulin-like growth factor 2 receptor Approved

Receptor Low Druggability

Drugs targeting IGF2R typically work by blocking IGF2 binding and signaling through the IGF1R/IGF2R axis, thereby inhibiting mitogenic and anti-apoptotic effects in cancer cells. Alternatively, agents may enhance IGF2 clearance through IGF2R-mediated endocytosis to reduce circulating IGF2 levels and downstream signaling.

PIEZO1 Piezo-type mechanosensitive ion channel component Phase I

Ion Channel Low Druggability

Small molecule modulator of mechanosensitive ion channel activity

ABCB1 P-glycoprotein Phase III

Transporter Medium Druggability

Small molecule inhibitors to reduce efflux pump activity and enhance CNS drug penetration

MLCK Myosin light chain kinase Phase II

Kinase Low Druggability

MLCK inhibitors block the phosphorylation of myosin light chains, thereby reducing cytoskeletal contraction and stabilizing tight junctions at the blood-brain barrier and endothelial surfaces. This mechanism reduces vascular permeability and preserves barrier integrity in conditions characterized by excessive leakage or cytoskeletal dysfunction.

PLA2G4A Phospholipase A2 group IVA Phase II

Enzyme Low Druggability

Small molecule inhibitor of cytosolic phospholipase A2 enzymatic activity

KDM6A Lysine demethylase 6A Phase I

Epigenetic Regulator Low Druggability

Small molecule inhibition of histone demethylase activity

COX4I1 Cytochrome C Oxidase Subunit 4I1 Phase II

Enzyme Low Druggability

Drugs targeting COX4I1 pathway would enhance electron transport chain efficiency or stabilize complex IV assembly, improving ATP production and reducing oxidative stress in mitochondria. These agents work by either promoting mitochondrial bioenergetics, acting as electron donors/acceptors, or preventing complex IV degradation in diseases with impaired oxidative phosphorylation.

ZO1 Zonula occludens-1 Approved

Structural Protein Low Druggability

Drugs targeting ZO1 typically work by stabilizing or modulating tight junction protein interactions, either by directly binding to ZO1 scaffolding domains or by regulating upstream signaling pathways that control ZO1 phosphorylation and localization. These approaches aim to restore blood-brain barrier integrity or modulate paracellular permeability depending on therapeutic context.

OCLN Occludin Approved

Structural Protein Low Druggability

Drugs targeting OCLN would stabilize or enhance tight junction protein interactions, reinforcing the structural integrity of the blood-brain barrier and reducing pathological barrier permeability. Therapeutic approaches would involve either direct protein stabilization or indirect modulation of occludin phosphorylation and trafficking to maintain barrier function.

CYP46A1 Cytochrome P450 Family 46 Subfamily A Member 1 Approved

Enzyme Medium Druggability

Small molecule activator of cholesterol 24-hydroxylase enhancing brain cholesterol turnover

TARDBP TAR DNA-binding protein 43 Phase III

Transcription Factor Low Druggability

RNA-binding and transcription regulation, challenging for small molecule targeting

NPM1 Nucleophosmin Phase III

Chaperone Low Druggability

Small molecule modulators of nucleolar function and protein interactions

SMPD1 Sphingomyelin phosphodiesterase 1 Approved

Enzyme Medium Druggability

Small molecule inhibitor or modulator of sphingomyelinase activity

SREBF2 Sterol regulatory element binding transcription fa Phase II

Transcription Factor Undruggable Druggability

Small molecule modulators of transcriptional activity or protein-protein interactions

CHMP2B Charged multivesicular body protein 2B Phase II

Other Low Druggability

Therapeutic agents targeting CHMP2B would modulate ESCRT-III complex function to enhance endosomal sorting and autophagy, potentially clearing protein aggregates associated with frontotemporal dementia or compensating for loss-of-function mutations. Strategies include antisense oligonucleotides to modulate protein expression, autophagy enhancers to promote cellular clearance pathways, or small molecules that stabilize ESCRT-III complex assembly and function.

NLGN1 Neuroligin-1 Phase II

Receptor Medium Druggability

Drugs targeting NLGN1 would modulate synaptic adhesion by either enhancing or blocking the neuroligin-neurexin interaction at the postsynaptic membrane, thereby regulating synapse formation, stabilization, and synaptic transmission. Indirect modulators may enhance GABAergic signaling or vasopressin-mediated pathways that influence neuroligin-dependent synaptic maturation and plasticity.

CERS2 Ceramide synthase 2 Phase II

Enzyme Low Druggability

CERS2 inhibitors would reduce the enzymatic synthesis of very long-chain ceramides by blocking the condensation of serine and palmitoyl-CoA, thereby decreasing ceramide-mediated neuroinflammation and apoptosis implicated in neurodegenerative pathology. This modulation of the ceramide signaling cascade may provide neuroprotective effects in Alzheimer's disease and related neurodegenerative conditions.

PYCARD Apoptosis-associated speck-like protein containing Phase II

Signaling Protein Low Druggability

PYCARD acts as a critical adaptor protein in inflammasome activation, facilitating pro-inflammatory caspase-1 recruitment and subsequent IL-1β/IL-18 processing, which contributes to neuroinflammatory processes in neurodegenerative conditions like Alzheimer's and Parkinson's disease. Its protein-protein interaction domains mediate inflammatory signal transduction, potentially amplifying neuronal damage through excessive immune response activation.

ST6GAL1 ST6 beta-galactoside alpha-2,6-sialyltransferase 1 Approved

Enzyme Low Druggability

ST6GAL1 inhibitors would block the addition of α2,6-linked sialic acids to N-glycans on cell surface proteins, altering immune cell recognition and potentially enhancing anti-tumor immunity or modulating inflammatory responses. This glycosylation modification is crucial for immune evasion in cancer and autoimmune disease pathogenesis.

PLIN2 Perilipin 2 Approved

Structural Protein Undruggable Druggability

Direct PLIN2 inhibitors would reduce lipid droplet formation and stability, promoting lipid mobilization and reducing pathological lipid accumulation. Indirect approaches target upstream regulators of PLIN2 expression or modulate associated lipases to alter lipid storage dynamics in metabolic and neurodegenerative disease states.

HSPG2 Heparan Sulfate Proteoglycan 2 Phase II

Structural Protein Low Druggability

Targeting protein-heparan sulfate interactions or enzymatic modification

DGAT1 Diacylglycerol O-Acyltransferase 1 Phase III

Enzyme Low Druggability

Small molecule inhibitor of triglyceride synthesis enzyme

SYNCRIP Heterogeneous nuclear ribonucleoprotein Q Phase II

Signaling Protein Low Druggability

Small molecule or antisense-based inhibitors would disrupt SYNCRIP's RNA-binding capability, reducing its ability to facilitate mRNA transport and local protein synthesis, potentially modulating disease pathways in neurological disorders or cancers where SYNCRIP dysfunction is implicated.

CHR2 Channelrhodopsin-2 Phase II

Ion Channel Low Druggability

CHR2 functions as a light-gated cation channel that opens in response to blue light (470nm), allowing depolarization through Na+ and Ca2+ influx. Therapeutic approaches would involve delivering CHR2 via gene therapy to degenerated neurons or photoreceptors, enabling light-dependent control of neural activity for vision restoration or neuromodulation applications.

FOXP3 Forkhead box protein P3 Phase I

Transcription Factor Low Druggability

Transcription factor modulation - no direct small molecule binding

SETX Senataxin Approved

Enzyme Low Druggability

Therapeutic agents targeting SETX would likely enhance RNA helicase activity or stabilize protein function to improve transcriptional regulation and DNA repair, or alternatively inhibit aberrant signaling pathways triggered by SETX dysfunction in neuronal tissues. Small molecule stabilizers or gene therapy approaches could restore deficient helicase activity in ataxia-causing mutations.

PLA2G6 Phospholipase A2 group VI Approved

Enzyme Low Druggability

Small molecule inhibitor of calcium-independent phospholipase A2 activity

SNAP25 Synaptosome associated protein 25 Approved

Structural Protein Low Druggability

Protein cleavage by botulinum toxin or small molecule modulators of SNARE complex formation

RELN Reelin Approved

Signaling Protein Low Druggability

Drugs targeting RELN would primarily work by enhancing reelin expression or signaling through its receptors (VLDLR and ApoER2) to promote neuronal migration, synaptic plasticity, and cognitive function. Alternatively, pathway modulators could enhance downstream signaling cascades (Dab1-mediated pathways) to compensate for reelin deficiency or dysfunction.

SGMS2 Sphingomyelin synthase 2 Phase III

Enzyme Low Druggability

SGMS2 inhibitors would block the enzymatic transfer of phosphocholine to ceramide, reducing sphingomyelin biosynthesis and altering membrane composition and cellular signaling. This modulation could reduce pathological lipid accumulation and restore normal cell membrane dynamics in diseases characterized by sphingolipid dysregulation.

MCU Mitochondrial calcium uniporter Phase III

Ion Channel Low Druggability

MCU inhibitors block the mitochondrial calcium uniporter channel, reducing excessive calcium accumulation in mitochondria that leads to oxidative stress, energy depletion, and cell death. This mechanism may protect against ischemic injury, neurodegeneration, and heart failure by preserving mitochondrial function and preventing apoptosis in calcium-sensitive tissues.

FUT8 Alpha-(1,6)-fucosyltransferase Phase II

Enzyme Low Druggability

FUT8 inhibitors would block the addition of core fucose to N-linked glycans on proteins, modulating antibody-dependent cellular cytotoxicity (ADCC) and potentially reducing pathological protein aggregation in neurodegenerative diseases. By preventing fucosylation, these drugs could enhance immune effector function or alter protein conformational stability and clearance.

GAP43 Growth associated protein 43 Approved

Structural Protein Undruggable Druggability

Drugs targeting GAP43 would enhance axonal growth cone formation and synaptic plasticity by promoting phosphorylation or membrane translocation of GAP43, thereby facilitating neurite outgrowth and synapse formation. Alternatively, agents could upregulate GAP43 expression to restore neuronal connectivity and compensate for age-related decline in neurodegenerative conditions.

SIRT1 NAD-dependent protein deacetylase sirtuin-1 Phase III

Epigenetic Regulator Medium Druggability

SIRT1 activation via NAD+ precursors or allosteric activators deacetylates tau (reducing aggregation), enhances mitophagy, and restores circadian gene expression

SGMS1 Sphingomyelin synthase 1 Approved

Enzyme Low Druggability

SGMS1 inhibitors would block the transfer of phosphocholine from phosphatidylcholine to ceramide, reducing sphingomyelin synthesis and potentially decreasing membrane rigidity and inflammatory signaling. This mechanism could modulate membrane-dependent cellular processes and may have therapeutic effects in lipid storage disorders and metabolic diseases.

AQP4 Aquaporin-4 Phase I

Ion Channel Low Druggability

Water channel inhibitor or modulator

FLOT1 Flotillin 1 Phase II

Structural Protein Low Druggability

Drug candidates would modulate FLOT1-mediated lipid raft organization and signaling platform assembly, thereby disrupting pathological protein trafficking and reducing amyloid-beta or tau-related pathology in neurodegenerative diseases. FLOT1 inhibitors would interfere with membrane scaffold formation necessary for aberrant signaling in neuroinflammatory and proteinopathic cascades.

CAV1 Caveolin-1 Approved

Structural Protein Low Druggability

No established drugging mechanism for structural membrane protein

LOXL1-4 Lysyl oxidase-like 1-4 Phase II

Enzyme Low Druggability

Small molecule enzyme inhibitors targeting the catalytic domain

BRD4 Bromodomain-containing protein 4 Phase II

Epigenetic Regulator Low Druggability

BRD4 inhibition reduces neuroinflammatory super-enhancer activity while biased BRD4 modulators can selectively restore neuroprotective gene expression

ST8SIA1 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltra Phase II

Enzyme Low Druggability

ST8SIA1 inhibitors would block the synthesis of polysialic acid chains on NCAM, reducing neural cell plasticity and potentially modulating neuroinflammatory responses. This mechanism could be therapeutically relevant for neurodevelopmental disorders or neuroinflammatory conditions where excessive polysialylation contributes to pathology.

CLDN5 Claudin-5 Approved

Structural Protein Undruggable Druggability

Tight junction protein modulation - no established druggable mechanisms

CLDN1 Claudin-1 Phase II

Structural Protein Undruggable Druggability

Tight junction protein modulation - no established druggable mechanisms

SLC16A2 Monocarboxylate transporter 8 Phase I

Transporter Low Druggability

Substrate supplementation or transporter modulation

CHMP4B Charged multivesicular body protein 4B Phase II

Other Low Druggability

CHMP4B-targeting drugs would inhibit or modulate ESCRT-III complex assembly and membrane scission, disrupting cellular degradation pathways (autophagy, lysosomal trafficking) and potentially inhibiting viral budding or cancer cell survival. Therapeutics could involve blocking protein-protein interactions within the ESCRT complex or stabilizing/destabilizing CHMP4B conformational states.

CNO Cappuccino Phase III

Other Low Druggability

No established druggable mechanisms

CSGA CSGA Protein Phase I

Protein Medium Druggability

Prioritized from 1 SciDEX hypotheses, including: Targeting Bacterial Curli Fibrils to Prevent α-Synuclein Cross-Seeding

MTOR Mechanistic Target of Rapamycin Phase I

Kinase Low Druggability

Prioritized from 1 SciDEX hypotheses, including: APOE-Dependent Autophagy Restoration

ST3GAL2 ST3 beta-galactoside alpha-2,3-sialyltransferase 2 Phase II

Enzyme Low Druggability

Inhibitors of ST3GAL2 would block the transfer of sialic acid (α-2,3 linkage) to galactose residues on glycoproteins and glycolipids, reducing cell surface sialylation and potentially enhancing immune recognition of cancer cells or modulating inflammatory responses. Alternatively, activators or substrate analogs could enhance sialylation for immune tolerance in inflammatory conditions.

GFAP Glial fibrillary acidic protein Phase II

Structural Protein Medium Druggability

Biomarker readout — GFAP levels reflect astrocyte reactivity; modulating upstream pathways (e.g., NF-κB, JAK-STAT) reduces GFAP expression

MAP6 Microtubule-associated protein 6 Phase II

Structural Protein Undruggable Druggability

Drugs targeting MAP6 would stabilize microtubules through direct binding or modulation of MAP6's stabilizing activity, thereby promoting neuronal cytoskeletal integrity and synaptic function. This stabilization could enhance axonal transport, prevent neuronal degeneration, and support cognitive and synaptic plasticity in neurodegenerative conditions.

GPR109A Hydroxycarboxylic Acid Receptor 2 (HCAR2)

Receptor Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Targeted Butyrate Supplementation for Microglial Phenotype Modulation

CHRNA7 CHRNA7 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain Anti-Inflammatory Communication

AADC Aromatic L-amino acid decarboxylase Approved

Enzyme Medium Druggability

Small molecule inhibitor preventing peripheral conversion of levodopa to dopamine

SIRT3 NAD-dependent deacetylase sirtuin-3, mitochondrial Phase II

Enzyme Medium Druggability

Enzyme activation — enhancing SIRT3 deacetylase activity restores mitochondrial protein function and reduces oxidative stress

CELL-TYPE-SPECIFICESSENTIALGENES CELL-TYPE-SPECIFICESSENTIALGENES Phase I

Signaling Protein Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Context-Dependent CRISPR Activation in Specific Neuronal Subtypes

PIEZO1ANDKCNK2 PIEZO1ANDKCNK2

Signaling Protein Medium Druggability

Prioritized from 1 SciDEX hypotheses, including: Mechanosensitive Ion Channel Reprogramming

Structural Protein Medium Druggability

Tau aggregation inhibitors, anti-tau antibodies, tau phosphorylation modulators

TRAK1_KIF5A Trafficking kinesin protein 1 / Kinesin family mem Phase II

Transporter Low Druggability

Therapeutic approaches targeting TRAK1_KIF5A aim to restore or enhance axonal mitochondrial transport by either stabilizing the KIF5A motor protein complex, reducing mutant protein expression through antisense oligonucleotides, or replacing defective protein via gene therapy. This restores cellular energy homeostasis and reduces neuronal degeneration in motor neurons.

OCT4 OCT4 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Partial Neuronal Reprogramming via Modified Yamanaka Cocktail

DGAT1ANDSOAT1 DGAT1ANDSOAT1

Signaling Protein Medium Druggability

Prioritized from 1 SciDEX hypotheses, including: Lipid Droplet Dynamics as Phenotype Switches

TFEB TFEB Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: The Mitochondrial-Lysosomal Metabolic Coupling Dysfunction

RHOT1 RHOT1 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Miro1-Mediated Mitochondrial Trafficking Enhancement Therapy

C4B C4B Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Age-Dependent Complement C4b Upregulation Drives Synaptic Vulnerability in Hippocampal CA1 Neurons

PHB2 PHB2 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Prohibitin-2 Mitochondrial Cross-Seeding Hub Disruption

ACSL4 Long-chain-fatty-acid--CoA ligase 4 Phase III

Enzyme Low Druggability

Enzyme inhibition — blocking ACSL4 prevents incorporation of PUFAs into membrane phospholipids, reducing ferroptosis susceptibility

PVALB Parvalbumin Phase II

Signaling Protein Low Druggability

No known druggable mechanism

DNAJB6 DNAJB6 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: HSP70 Co-chaperone DNAJB6 Universal Cross-Seeding Inhibitor

SYNTHETIC SYNTHETIC Protein

Protein other Druggability

DISEASE-CAUSING DISEASE-CAUSING Protein

Protein other Druggability

CELL-TYPE-SPECIFIC CELL-TYPE-SPECIFIC Protein

Protein other Druggability

SLC17A7 Vesicular glutamate transporter 1 (VGLUT1) Phase III

Transporter Medium Druggability

Expression restoration — upregulating SLC17A7 transcription or stabilizing VGLUT1 protein to preserve excitatory synaptic function

SPTLC1 SPTLC1 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: APOE-Mediated Synaptic Lipid Raft Stabilization

NURR1 NURR1 Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Programmable Neuronal Circuit Repair via Epigenetic CRISPR

TDC TDC Protein Approved

Protein Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Restoring Neuroprotective Tryptophan Metabolism via Targeted Probiotic Engineering

MITOCHONDRIALBIOGENESISGENES MITOCHONDRIALBIOGENESISGENES Phase I

Signaling Protein Medium Druggability

Prioritized from 1 SciDEX hypotheses, including: Metabolic Reprogramming via Coordinated Multi-Gene CRISPR Circuits

AGER AGER Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Blocking AGE-RAGE Signaling in Enteric Glia to Prevent Neuroinflammatory Cascade

SLC16A1 Monocarboxylate transporter 1 (MCT1) Phase II

Transporter Low Druggability

Transporter modulation — restoring MCT1/MCT4 balance to normalize astrocyte-neuron metabolic coupling

PGC1A PGC1A Protein

Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Metabolic Reprogramming via Coordinated Multi-Gene CRISPR Circuits

Signaling Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Programmable Neuronal Circuit Repair via Epigenetic CRISPR

DISEASE-CAUSINGMUTATIONSWITHINTEGRATEDREPORTERS DISEASE-CAUSINGMUTATIONSWITHINTEGRATEDREPORTERS Phase I

Signaling Protein Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Multi-Modal CRISPR Platform for Simultaneous Editing and Monitoring

Signaling Protein Undruggable Druggability

Prioritized from 1 SciDEX hypotheses, including: Microglia-Derived Extracellular Vesicle Engineering for Targeted Mitochondrial Delivery

SYNTHETICFUSIONPROTEINS SYNTHETICFUSIONPROTEINS Phase I

Signaling Protein Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Synthetic Biology Approach: Designer Mitochondrial Export Systems

NEURONALIDENTITYTRANSCRIPTIONFACTORS NEURONALIDENTITYTRANSCRIPTIONFACTORS Phase I

Signaling Protein Low Druggability

Prioritized from 1 SciDEX hypotheses, including: Programmable Neuronal Circuit Repair via Epigenetic CRISPR