TRPM8

Summary

TRPM8 (transient receptor potential cation channel subfamily M member 8, HGNC:17961) is a protein-coding gene on chromosome 2q37.1, encoding Transient receptor potential cation channel subfamily M member 8 (Q7Z2W7). Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+).

Predicted to enable ligand-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within several processes, including intracellular calcium ion homeostasis; response to cold; and thermoception. Located in plasma membrane.

Source: NCBI Gene 79054 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 168 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17961
Approved symbol	TRPM8
Name	transient receptor potential cation channel subfamily M member 8
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144481
Ensembl biotype	protein_coding
OMIM	606678
Entrez	79054

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000324695, ENST00000355722, ENST00000409625, ENST00000433712, ENST00000439148, ENST00000444298, ENST00000456930, ENST00000466594, ENST00000475044, ENST00000477103, ENST00000477698, ENST00000479332, ENST00000487033, ENST00000490797

RefSeq mRNA: 19 — MANE Select: NM_024080 NM_001397606, NM_001397607, NM_001397608, NM_001397609, NM_001397610, NM_001397611, NM_001397612, NM_001397613, NM_001397614, NM_001397615, NM_001397617, NM_001397620, NM_001397621, NM_001397622, NM_001397627, NM_001397628, NM_001397629, NM_001397630, NM_024080

CCDS: CCDS33407, CCDS92975, CCDS92976

Canonical transcript exons

ENST00000324695 — 26 exons

Exon	Start	End
ENSE00001073225	233970210	233970426
ENSE00001460423	234017299	234019522
ENSE00003462266	233963282	233963377
ENSE00003467837	233964628	233964757
ENSE00003476247	233966610	233966755
ENSE00003478447	233996326	233996516
ENSE00003478895	233969695	233969807
ENSE00003492390	234006853	234006952
ENSE00003496197	233960776	233961066
ENSE00003504435	233926533	233926654
ENSE00003504759	233938998	233939175
ENSE00003508543	233983053	233983224
ENSE00003510303	233937353	233937509
ENSE00003511324	234008070	234008103
ENSE00003520256	233985688	233985865
ENSE00003535519	233945856	233946030
ENSE00003552613	233955132	233955250
ENSE00003580477	233930668	233930741
ENSE00003583340	234014562	234014654
ENSE00003604911	233942576	233942748
ENSE00003630914	233953917	233954019
ENSE00003687061	233949949	233950146
ENSE00003689429	233980188	233980279
ENSE00003692846	233981774	233981915
ENSE00003719704	233947088	233947155
ENSE00003849141	233917373	233917432

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 87.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7089 / max 171.2967, expressed in 144 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26108	0.1566	43
26124	0.1304	9
26116	0.1067	49
26123	0.0650	9
26121	0.0558	11
26111	0.0297	2
26115	0.0292	6
26113	0.0255	1
26120	0.0238	10
26122	0.0208	8

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	87.64	gold quality
liver	UBERON:0002107	87.48	gold quality
prostate gland	UBERON:0002367	87.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.59	gold quality
pancreatic ductal cell	CL:0002079	67.38	silver quality
trigeminal ganglion	UBERON:0001675	63.93	gold quality
heart right ventricle	UBERON:0002080	62.23	gold quality
endothelial cell	CL:0000115	60.76	gold quality
secondary oocyte	CL:0000655	60.73	gold quality
parotid gland	UBERON:0001831	60.66	gold quality
tibialis anterior	UBERON:0001385	60.03	silver quality
amniotic fluid	UBERON:0000173	59.56	silver quality
deltoid	UBERON:0001476	59.15	gold quality
triceps brachii	UBERON:0001509	58.71	gold quality
gluteal muscle	UBERON:0002000	58.57	gold quality
biceps brachii	UBERON:0001507	58.35	gold quality
nasal cavity epithelium	UBERON:0005384	58.01	gold quality
islet of Langerhans	UBERON:0000006	57.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.89	silver quality
endometrium	UBERON:0001295	54.91	gold quality
quadriceps femoris	UBERON:0001377	54.30	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	53.73	gold quality
testis	UBERON:0000473	52.96	gold quality
vastus lateralis	UBERON:0001379	52.89	gold quality
left testis	UBERON:0004533	52.20	gold quality
myocardium	UBERON:0002349	51.72	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.43	gold quality
left ventricle myocardium	UBERON:0006566	51.17	gold quality
right testis	UBERON:0004534	51.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	51.07	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

92 targeting TRPM8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3121-3P	99.82	71.96	3630

Literature-anchored findings (GeneRIF, showing 40)

• temperature sensing is tightly linked to voltage-dependent gating in the cold-sensitive channel TRPM8 and the heat-sensitive channel TRPV1 (PMID:15306801)
• characterize the cold- and voltage-induced activation of TRPM8 channel in an attempt to identify the temperature- and voltage-dependent components involved in channel activation (PMID:15492228)
• TRPM8 gene expression requires a functional androgen receptor. (PMID:15947109)
• In conclusion, our results indicate that menthol induced steep outward rectification of TRPM8 results from the voltage-dependent open channel probability and the permeating ion-dependent modulation of the unitary channel conductance. (PMID:15950184)
• results directly demonstrate that expression of TRPM8 in mammalian neurones induces cold sensing. (PMID:15961432)
• TRPM8 may be an ER Ca(2+) release channel, involved in a number of Ca(2+)- and store-dependent processes in prostate cancer epithelial cells, including those that are important for prostate carcinogenesis, such as proliferation and apoptosis. (PMID:16174775)
• investigated maturation of TRPM8 by identifying and mutating relevant N-linked glycosylation site and showing that glycosylation is neither essential for multimerization nor for transport to the plasma membrane (PMID:17065148)
• TRPM8-independent menthol-induced Ca2+ release originates from both endoplasmic reticulum and Golgi compartments. (PMID:17142461)
• TRPM8 is now best known as a cold- and menthol-activated channel implicated in thermosensation–{REVIEW} (PMID:17217067)
• Expression TRPM8 in neuroendocrine tumor cells and its role in regulating Ca(2+) and NT secretion. (PMID:17426390)
• The same regulatory events have opposing actions on TRPM8 and TRPV1 receptors. Anandamide and NADA are the first potential endogenous functional antagonists of TRPM8 channels. (PMID:17428469)
• Prostate cancer (PCa) epithelial cells obtained from in situ PCa were characterized by a significantly stronger plasma membrane TRPM8-mediated current than that in normal cells. (PMID:17510704)
• Study represent new tools to dissect TRPM8 functions and may serve as chemical leads for the development of additional TRPM8 agonists and novel antagonists. (PMID:17517434)
• accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. (PMID:17521436)
• the transmembrane segment S6 has a role in determining cation versus anion selectivity of TRPM2 and TRPM8 (PMID:17604279)
• TRPM8 axons diffusely innervate the skin and oral cavity of TRPM8 transgenic mice, terminating in nerve endings mediating distinct perceptions of innocuous cool, noxious cold, and first- and second-cold pain. (PMID:18094254)
• The expression of TRPM8 mRNA in the prostate was much higher than that in the bladder mucosa (3024:1), but was not found in the bladder muscle layer. (PMID:18384850)
• In patients suffering from cold allodynia following cold injury, no evidence is found for sensitization of TRPM8 or TRPA1 or pathologic expression of TRPM8 on silent afferent C-fiber nociceptors. (PMID:18440147)
• activation of the TRPM8 variant in human lung epithelial cells leads to increased expression of IL-1alpha, -1beta, -4, -6, -8, and -13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-alpha. (PMID:18441098)
• TRPM8 variant receptor may function as a modulator of respiratory physiology caused by cold air, and may partially explain asthmatic respiratory hypersensitivity to cold air. (PMID:18458237)
• TRPM8 plays a role in mechanisms that increase Ca(2+) needed for DBTRG cell migration. (PMID:18485891)
• results reveal that a functional TRPM8 protein is expressed in human melanoma cells to involve the mechanism underlying tumor progression via the Ca(2+) handling pathway, providing us with a novel target of drug development for malignant melanoma (PMID:18524940)
• icilin specifically inhibits TRPM8 independently of its interaction site within the S2-S3 linker through a process distinct from desensitization. (PMID:19095656)
• Pore dilation occurs in TRPA1, but not in TRPM8 channels. (PMID:19159452)
• analysis of the quaternary structure suggests that the N-terminus possesses a solenoidal topology which could be involved in tetramerization due to its electrostatic characteristics (PMID:19230823)
• TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer. (PMID:19234481)
• TRPM8 channels may contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms. (PMID:19363131)
• TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity. (PMID:19404398)
• The reduction of TRPV2 and TRPM8 immunoreactive nerve fibers in skin from individuals with Norrbottnian congenital insensitivity to pain further suggests that these ion channels are expressed primarily on nociceptive primary sensory neurons. (PMID:19482060)
• mRNA for TRPA1 and TRPM8 are strongly upregulated in differentiating IMR-32 cells. (PMID:19507192)
• TRPM8 is a thermosensitive channel in human sperm that could be involved in cell signaling events such as thermotaxis or chemotaxis (PMID:19582168)
• tissue TRPM8 mRNA levels can be used for detection of prostate cancer, urine and blood TRPM8 mRNA levels may prove to be useful for distinguishing metastatic disease from clinically localized prostate cancer (PMID:20043080)
• TRPM8 is inhibited via the alpha 2A adrenoreceptor signaling pathway (PMID:20110357)
• TRPM8 channels are expressed and functional in breast cancer and their expression is regulated by estrogen receptor-alpha. (PMID:20482834)
• PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis. (PMID:20531306)
• the gating processes in TRPM2 and TRPM8 differ in their requirements for specific structures within the pore. (PMID:20587417)
• Results indicate that TRPM8 is aberrantly over-expressed in pancreatic adenocarcinoma and required for cellular proliferation. (PMID:20605675)
• Studies indicate that TRPM8 expressed both in the apical epithelial cells and in the smooth muscle cells of the prostate. (PMID:20730379)
• Removing cholesterol with methyl-beta-cyclodextrin (MbetaCD) stabilizes TRPM8 motion in the PM and is correlated with larger TRPM8 current amplitude that results from an increase in the number of available channels without a change in open probability (PMID:20948964)
• forced overexpression of human TRPM8 facilitated the trafficking of TRPM8 channels residing in the endoplasmic reticulum to the plasma membrane, leading to a marked potentiation in the efficacy of the different blockers. (PMID:21052713)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trpm8	ENSMUSG00000036251
rattus_norvegicus	Trpm8	ENSRNOG00000019035
drosophila_melanogaster	Trpm	FBGN0265194
caenorhabditis_elegans		WBGENE00000425
caenorhabditis_elegans	gon-2	WBGENE00001651
caenorhabditis_elegans		WBGENE00004149
caenorhabditis_elegans		WBGENE00020972
caenorhabditis_elegans		WBGENE00021404
caenorhabditis_elegans		WBGENE00021408

Paralogs (7): TRPM5 (ENSG00000070985), TRPM3 (ENSG00000083067), TRPM7 (ENSG00000092439), TRPM6 (ENSG00000119121), TRPM4 (ENSG00000130529), TRPM1 (ENSG00000134160), TRPM2 (ENSG00000142185)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily M member 8 — Q7Z2W7 (reviewed: Q7Z2W7)

Alternative names: Long transient receptor potential channel 6, Transient receptor potential p8

All UniProt accessions (8): Q7Z2W7, A0A0A0MSV2, A0A0C4DFT0, A0A1L1Z822, F8WD55, H0Y7P0, H7BZP4, W8DTH1

UniProt curated annotations — full annotation on UniProt →

Function. Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+). Activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. Activated by cool temperatures (<23-28 degrees Celsius) and by chemical ligands evoking a sensation of coolness, such as menthol and icilin therefore plays a central role in the detection of environmental cold temperatures. TRPM8 is a voltage-dependent channel; its activation by cold or chemical ligands shifts its voltage thresholds towards physiological membrane potentials, leading to the opening of the channel. In addition to its critical role in temperature sensing, regulates basal tear secretion by sensing evaporation-induced cooling and changes in osmolality. May plays a role in prostate cancer cell migration. Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel. Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.

Subunit / interactions. Homotetramer. Isoform 2 and isoform 3 interact with the C-terminus of isoform 1 in a thermosensitive manner with decreased interaction at 21 degrees Celsius compared to 37 degrees Celsius. Interacts (via N-terminus and C-terminus domains) with TCAF1; the interaction stimulates TRPM8 channel activity. Interacts (via N-terminus and C-terminus domains) with TCAF2 isoform 2; the interaction inhibits TRPM8 channel activity.

Subcellular location. Cell membrane. Membrane raft. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in prostate. Also expressed in prostate tumors and in non-prostatic primary tumors such as colon, lung, breast and skin tumors.

Activity regulation. Activated by cold temperatures and by both natural and synthetic cooling compounds such as menthol and icilin. Activation of the channel requires the presence of PI(4,5)P2. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels. Activated by intracellular Ca(2+).

Domain organisation. The coiled coil region is required for multimerization. Cooling agents bind within a pocket formed entirely by the S1-S4 helices that opens to the cytoplasm.

Miscellaneous. Its expression in most prostate tumors as well as the presence of an immunogenic epitope suggest that it may be suitable for the design of peptide vaccination strategies for prostate cancers.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z2W7-1	1	yes
Q7Z2W7-2	2, sTRPM8-18, sM8-18
Q7Z2W7-3	3, sTRPM8-6, sM8-6
Q7Z2W7-4	4

RefSeq proteins (19): NP_001384535, NP_001384536, NP_001384537, NP_001384538, NP_001384539, NP_001384540, NP_001384541, NP_001384542, NP_001384543, NP_001384544, NP_001384546, NP_001384549, NP_001384550, NP_001384551, NP_001384556, NP_001384557, NP_001384558, NP_001384559, NP_076985* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005821	Ion_trans_dom	Domain
IPR041491	TRPM_SLOG	Domain
IPR050927	TRPM	Family
IPR057366	TRPM-like	Domain

Pfam: PF00520, PF18139, PF25508

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (126 total): helix 47, strand 25, mutagenesis site 11, topological domain 8, splice variant 7, transmembrane region 6, sequence variant 6, turn 4, binding site 4, sequence conflict 3, chain 1, intramembrane region 1, region of interest 1, coiled-coil region 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8BDC	ELECTRON MICROSCOPY	2.65
9ZCU	ELECTRON MICROSCOPY	2.86
9P8Y	ELECTRON MICROSCOPY	3
9PB5	ELECTRON MICROSCOPY	3.5
9ZCV	ELECTRON MICROSCOPY	3.65
9ZF0	ELECTRON MICROSCOPY	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2W7-F1	80.42	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 782; 785; 799; 802

Glycosylation sites (1): 934

Mutagenesis-validated functional residues (11):

Position	Phenotype
745	abolishes ion channel activity to cold stimulis.
746	does not affect ion channel activity to cold stimulis.
799	abolishes ion channel activity activation by icilin. does not affect ion channel activity activation by menthol or cooli
802	decreases ion channel sensitivity to cold stimulis.
821	no effect on glycosylation or ability to form functional channels.
934	abolishes glycosylation.
946	no effect on glycosylation or channel activity.
995	decreases in sensitivity to pi(4,5)p2.
998	decreases in sensitivity to pi(4,5)p2. insensitive to icilin.
1008	decreases in sensitivity to pi(4,5)p2. reduced the sensitivity of the channel to menthol stimulation. insensitive to ici
1089	abolishes multimerization and channel activity. reduces cell surface expression.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 108 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_RESPONSE_TO_COLD, GOCC_CELL_SURFACE, RACCACAR_AML_Q6, LHX3_01, GOBP_MONOATOMIC_CATION_TRANSPORT, AML_Q6, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_PERCEPTION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (11): intracellular calcium ion homeostasis (GO:0006874), response to cold (GO:0009409), thermoception (GO:0050955), calcium ion transmembrane transport (GO:0070588), positive regulation of cold-induced thermogenesis (GO:0120162), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), response to temperature stimulus (GO:0009266), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): calcium channel activity (GO:0005262), identical protein binding (GO:0042802), metal ion binding (GO:0046872), ligand-gated calcium channel activity (GO:0099604), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), metal ion transmembrane transporter activity (GO:0046873)

GO Cellular Component (7): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), plasma membrane raft (GO:0044853), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Stimuli-sensing channels	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
metal ion transport	2
plasma membrane	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to stress	1
response to temperature stimulus	1
sensory perception of temperature stimulus	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
response to abiotic stimulus	1
intracellular signaling cassette	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
protein binding	1
cation binding	1
calcium channel activity	1
calcium-mediated signaling	1
ligand-gated monoatomic cation channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
monoatomic cation transmembrane transporter activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cell surface	1
side of membrane	1
membrane raft	1
plasma membrane region	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPM8	TRPV1	Q8NER1	995
TRPM8	TRPA1	O75762	984
TRPM8	TRPV3	Q8NET8	972
TRPM8	TRPV2	Q9Y5S1	929
TRPM8	TRPV4	Q9HBA0	889
TRPM8	ANK1	P16157	867
TRPM8	ANK3	Q12955	802
TRPM8	ANK2	Q01484	801
TRPM8	KNG1	P01042	798
TRPM8	TRPV6	Q9H1D0	751
TRPM8	GPR55	Q9Y2T6	747
TRPM8	NGF	P01138	726
TRPM8	FOLH1	Q04609	713
TRPM8	TRPV5	Q9NQA5	698
TRPM8	GPR18	Q14330	671

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TRPM8	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
TRPM8	TMBIM6	psi-mi:“MI:0914”(association)	0.350
CKAP2	WDR46	psi-mi:“MI:0914”(association)	0.350
TRPM8	STX5	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): AKAP5 (Affinity Capture-Western), TRPM8 (Affinity Capture-Western), TRPM4 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), STX5 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), TMBIM6 (Affinity Capture-MS), TRPM8 (Proximity Label-MS), TRIM4 (Affinity Capture-Western), TRPM8 (Affinity Capture-Western), UBA1 (Affinity Capture-Western), TRPM8 (Affinity Capture-Western), TRIM4 (Reconstituted Complex), TRPM8 (Reconstituted Complex), TRIM4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IMY7, A0JPA0, A2AP18, A8DYE2, J9SQF3, O00329, O35904, O75038, P0C1Q3, P0C588, P19687, P33402, P48736, P97557, Q02108, Q09M05, Q148L1, Q1LWG4, Q2TV84, Q2WEA5, Q3USB7, Q4ZHS0, Q502J0, Q5EBA1, Q60565, Q62688, Q69ZF7, Q6P4Q7, Q6PA06, Q7L5N7, Q7TN37, Q7Z2W7, Q7Z4N2, Q80YD1, Q8BTI9, Q8BYI6, Q8BZN2, Q8CIR4, Q8NHH9, Q8R455

Diamond homologs: A0A0R4IMY7, A7T1N0, A8DYE2, E9PTA2, J9SQF3, O94759, Q2TV84, Q2WEA5, Q5XIG0, Q7TN37, Q7Z2W7, Q7Z4N2, Q8BVU5, Q8R455, Q8R4D5, Q8TD43, Q91YD4, Q9BW91, Q9ESQ5, Q9HCF6, Q9JJH7, Q9NZQ8, S5UH55, Q09297, Q8CIR4, Q923J1, Q925B3, Q96QT4, Q9BX84, Q93971

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	TRPM8	phosphorylation
PPP2CA	“down-regulates activity”	TRPM8	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

168 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

4534 predictions. Top by Δscore:

Variant	Effect	Δscore
2:233926519:A:AG	acceptor_gain	1.0000
2:233926520:A:G	acceptor_gain	1.0000
2:233937336:A:AG	acceptor_gain	1.0000
2:233937337:C:G	acceptor_gain	1.0000
2:233938992:CCATA:C	acceptor_loss	1.0000
2:233938993:CATAG:C	acceptor_loss	1.0000
2:233938994:A:AG	acceptor_gain	1.0000
2:233938994:ATAGT:A	acceptor_loss	1.0000
2:233938995:T:G	acceptor_gain	1.0000
2:233938995:TAG:T	acceptor_loss	1.0000
2:233938996:A:AG	acceptor_gain	1.0000
2:233938996:AG:A	acceptor_loss	1.0000
2:233938997:G:GA	acceptor_gain	1.0000
2:233938997:G:T	acceptor_loss	1.0000
2:233938997:GT:G	acceptor_gain	1.0000
2:233938997:GTA:G	acceptor_gain	1.0000
2:233938997:GTAT:G	acceptor_gain	1.0000
2:233938997:GTATA:G	acceptor_gain	1.0000
2:233939175:GGTGA:G	donor_loss	1.0000
2:233939176:G:T	donor_loss	1.0000
2:233939177:T:G	donor_loss	1.0000
2:233942570:TGACA:T	acceptor_loss	1.0000
2:233942571:GACA:G	acceptor_loss	1.0000
2:233942572:ACAG:A	acceptor_loss	1.0000
2:233942573:CAGG:C	acceptor_loss	1.0000
2:233942574:A:AT	acceptor_loss	1.0000
2:233942733:G:GT	donor_gain	1.0000
2:233942734:A:T	donor_gain	1.0000
2:233946002:G:GT	donor_gain	1.0000
2:233947156:G:GG	donor_gain	1.0000

AlphaMissense

7349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:233942581:T:A	W178R	1.000
2:233942581:T:C	W178R	1.000
2:233966681:T:A	W651R	1.000
2:233966681:T:C	W651R	1.000
2:233930705:G:C	R52P	0.999
2:233939005:G:C	R119P	0.999
2:233939074:C:A	P142H	0.999
2:233939080:T:C	L144P	0.999
2:233942698:T:A	W217R	0.999
2:233942698:T:C	W217R	0.999
2:233945947:A:T	D264V	0.999
2:233955177:T:C	L430P	0.999
2:233955189:T:C	L434P	0.999
2:233955245:T:A	W453R	0.999
2:233955245:T:C	W453R	0.999
2:233960786:T:C	L458P	0.999
2:233960807:C:A	A465D	0.999
2:233960810:T:C	L466P	0.999
2:233960834:T:A	V474D	0.999
2:233960939:T:C	L509P	0.999
2:233963327:T:A	W567R	0.999
2:233963327:T:C	W567R	0.999
2:233963369:T:A	W581R	0.999
2:233963369:T:C	W581R	0.999
2:233964650:C:A	A591D	0.999
2:233964668:T:C	L597P	0.999
2:233964671:T:C	L598P	0.999
2:233964751:G:C	A625P	0.999
2:233966709:C:A	A660E	0.999
2:233966733:T:C	F668S	0.999

dbSNP variants (sampled 300 via entrez): RS1000023538 (2:233994826 C>G), RS1000052652 (2:233944553 T>C), RS1000080152 (2:234005483 C>G), RS1000106447 (2:233938178 G>A), RS1000119073 (2:233943382 G>A), RS1000203649 (2:233976773 C>T), RS1000280862 (2:234009538 C>A), RS1000290672 (2:233932184 A>G), RS1000324910 (2:233934537 C>A,G,T), RS1000327627 (2:233940471 T>A,C), RS1000363921 (2:233972457 G>A,T), RS1000368062 (2:234015950 T>C), RS1000380128 (2:233940714 G>A), RS1000465156 (2:233926331 G>A), RS1000487648 (2:233989502 C>T)

Disease associations

OMIM: gene MIM:606678 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001105_2	Migraine	6.000000e-12
GCST001563_4	Migraine	1.000000e-12
GCST002078_10	Migraine without aura	9.000000e-11
GCST002079_31	Migraine - clinic-based	1.000000e-08
GCST002080_3	Migraine with aura	1.000000e-07
GCST002081_20	Migraine	9.000000e-14
GCST002247_3	Blood pressure measurement (cold pressor test)	3.000000e-08
GCST002247_7	Blood pressure measurement (cold pressor test)	7.000000e-07
GCST002337_116	Amyotrophic lateral sclerosis (sporadic)	4.000000e-06
GCST003478_1	Hair greying	7.000000e-06
GCST003720_15	Migraine	3.000000e-09
GCST003720_24	Migraine	1.000000e-23
GCST003721_2	Migraine without aura	1.000000e-09
GCST003831_5	Asthma	3.000000e-06
GCST003832_15	Asthma (childhood onset)	9.000000e-06
GCST003986_3	Migraine	7.000000e-19
GCST005337_3	Headache	6.000000e-16
GCST007938_3	Medication use (anilides)	2.000000e-11
GCST007939_3	Medication use (antimigraine preparations)	9.000000e-15
GCST008817_1	Bilirubin levels	1.000000e-10
GCST009391_2092	Metabolite levels	5.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005404	response to cold pressor test
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0009938	Anilide use measurement
EFO:0009939	Antimigraine preparation use measurement
EFO:0004570	bilirubin measurement
EFO:0010373	phosphatidylcholine 32:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075319 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 611,295 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL256087	MENTHOL	4	182,803
CHEMBL294199	CAPSAICIN	4	52,939
CHEMBL465	DRONABINOL	4	62,107
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL258405	ICILLIN	3	1,025
CHEMBL470670	LEVOMENTHOL	3	182,553
CHEMBL207433	SB-705498	2	127
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL2441929	ACOLTREMON	2	1,169
CHEMBL3682589	ELISMETREP	2	88
CHEMBL497318	CANNABIGEROL	2	11,097
CHEMBL3577885	PF-05105679	1	23

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10166942	TRPM8		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
PBMC	Inhibition	9.3	pIC50
elismetrep	Antagonist	9.05	pIC50
M8-B	Pore blocker	8.1	pIC50
KPR-5714	Antagonist	7.6	pIC50
PF-05105679	Antagonist	6.99	pIC50
icilin	Agonist	6.9	pEC50
cannabigerol	Antagonist	6.8	pIC50
phytocannabinoid 6 [PMID: 38408345]	Antagonist	6.1	pIC50
BCTC	Antagonist	6.1	pIC50
scutellarein	Channel blocker	5.77	pIC50
cannabidiol	Antagonist	5.55	pIC50
cannabigeroquinone	Antagonist	5.52	pIC50
frescolat ML	Partial agonist	5.5	pEC50
thio-BCTC	Antagonist	5.5	pIC50
WS-3	Partial agonist	5.4	pEC50
frescolat MGA	Partial agonist	5.3	pEC50
cooling agent 10	Partial agonist	5.2	pEC50
2-APB	Antagonist	5.1	pIC50
acoltremon	Full agonist	4.9	pEC50
tacrolimus	Agonist	4.85	pEC50
(+)-menthol	Partial agonist	4.8	pEC50
capsazepine	Antagonist	4.7	pIC50
WS-5	Full agonist	4.6	pEC50
(-)-menthol	Activator	4.6	pEC50
PMD38	Partial agonist	4.5	pEC50

Binding affinities (BindingDB)

333 measured of 333 human assays (335 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(4-cyclopropylisoquinolin-3-yl)-4-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.3 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-3-methyl-4-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.3 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-3-methyl-4-(1H-1,2,4-triazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.5 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-3-methyl-4-(5-oxo-1,2,4-oxadiazolidin-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.5 nM	US-9487488: Sulfonamide compound
4-[[3-chloro-4-[cyclopropyl(difluoro)methyl]phenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	0.6 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-4-(5-methyl-1H-1,2,4-triazol-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.6 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-6-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]pyridine-3-sulfonamide	IC50	0.7 nM	US-9487488: Sulfonamide compound
N-(1-cyclopropyl-4-methylisoquinolin-3-yl)-4-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	0.7 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-4-(5-methyl-1H-1,2,4-triazol-3-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	0.7 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-3-methylbenzoic acid	IC50	0.7 nM	US-9487488: Sulfonamide compound
sodium 4-[[4-[cyclopropyl(difluoro)methyl]-3-fluorophenyl]methyl-(4-cyclopropylisoquinolin-3-yl)sulfamoyl]benzoate	IC50	0.8 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-3-methyl-4-(5-methyl-1H-1,2,4-triazol-3-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	0.8 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]benzoic acid	IC50	0.9 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
sodium 4-[[3-chloro-4-[cyclopropyl(difluoro)methyl]phenyl]methyl-[4-(trifluoromethyl)isoquinolin-3-yl]sulfamoyl]benzoate	IC50	0.9 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-4-(tetrazolidin-5-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	0.9 nM	US-9487488: Sulfonamide compound
4-[[3-chloro-4-[cyclopropyl(difluoro)methyl]phenyl]methyl-(1-cyclopropyl-4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[[4-[difluoro-(1-methylcyclopropyl)methyl]phenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-4-(5-oxo-1,2,4-oxadiazolidin-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	IC50	1 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-3-methyl-4-(1H-1,2,4-triazol-5-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	1 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-fluorobenzoic acid	IC50	1 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[(4,6-difluoro-1-benzothiophen-2-yl)methyl]sulfamoyl]benzoic acid	IC50	1.1 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
US9487488, 4	IC50	1.1 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-6-(5-oxo-1,2,4-oxadiazolidin-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]pyridine-3-sulfonamide	IC50	1.1 nM	US-9487488: Sulfonamide compound
4-(5-methyl-1H-1,2,4-triazol-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]-N-[4-(trifluoromethyl)isoquinolin-3-yl]benzenesulfonamide	IC50	1.1 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-6-(5-methyl-1H-1,2,4-triazol-3-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]pyridine-3-sulfonamide	IC50	1.1 nM	US-9487488: Sulfonamide compound
N-(4-cyclopropylisoquinolin-3-yl)-4-(5-oxo-1,2,4-oxadiazolidin-3-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	1.1 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-(methylamino)benzoic acid	IC50	1.1 nM	US-9487488: Sulfonamide compound
sodium 4-[[3-chloro-4-[cyclopropyl(difluoro)methyl]phenyl]methyl-(4-cyclopropylisoquinolin-3-yl)sulfamoyl]benzoate	IC50	1.2 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-4-(1H-1,2,4-triazol-5-yl)-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]benzenesulfonamide	IC50	1.2 nM	US-9487488: Sulfonamide compound
4-[(1,1-dimethyl-2,3-dihydroinden-5-yl)methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.3 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[(4,6-difluoro-1-benzothiophen-2-yl)methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.3 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[[3-chloro-4-[cyclopropyl(difluoro)methyl]phenyl]methyl-(3-methylquinolin-2-yl)sulfamoyl]benzoic acid	IC50	1.4 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-methylbenzoic acid	IC50	1.4 nM	US-9487488: Sulfonamide compound
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-(methoxymethyl)benzoic acid	IC50	1.4 nM	US-9487488: Sulfonamide compound
N-[4-[3,5-dichloro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.45 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
4-[[4-[cyclopropyl(difluoro)methyl]-3-fluorophenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.5 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-fluoro-6-methylbenzoic acid	IC50	1.5 nM	US-9487488: Sulfonamide compound
4-[[3-chloro-4-(1,1,1-trifluoro-2-methoxypropan-2-yl)phenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.6 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
sodium 4-[[4-[cyclopropyl(difluoro)methyl]-3-fluorophenyl]methyl-[4-(trifluoromethyl)isoquinolin-3-yl]sulfamoyl]benzoate	IC50	1.6 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
6-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]-N-[4-(trifluoromethyl)isoquinolin-3-yl]pyridine-3-sulfonamide	IC50	1.6 nM	US-9487488: Sulfonamide compound
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.68 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
4-[[4-[cyclobutyl(difluoro)methyl]phenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.7 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[[4-(1,1,1,3,3,3-hexafluoro-2-methoxypropan-2-yl)phenyl]methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.7 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
N-(4-cyclopropylisoquinolin-3-yl)-6-(1H-1,2,4-triazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]pyridine-3-sulfonamide	IC50	1.7 nM	US-9487488: Sulfonamide compound
4-[(4-tert-butylphenyl)methyl-(4-methylisoquinolin-3-yl)sulfamoyl]benzoic acid	IC50	1.8 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
sodium 4-[(1-cyclopropyl-4-methylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]benzoate	IC50	1.9 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[[4-(trifluoromethoxy)phenyl]methyl-[4-(trifluoromethyl)isoquinolin-3-yl]sulfamoyl]benzoic acid	IC50	2 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]-N-[4-(trifluoromethyl)isoquinolin-3-yl]benzenesulfonamide	IC50	2 nM	US-9487488: Sulfonamide compound
4-[(4-methylisoquinolin-3-yl)-[5-(trifluoromethoxy)-2,3-dihydro-1H-inden-1-yl]sulfamoyl]benzoic acid	IC50	2.1 nM	US-8987445: Sulfonamide compounds having TRPM8 antagonistic activity
4-[(4-cyclopropylisoquinolin-3-yl)-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]-2-ethylbenzoic acid	IC50	2.1 nM	US-9487488: Sulfonamide compound

ChEMBL bioactivities

799 potent at pChembl≥5 of 877 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL5287633
9.70	EC50	0.2	nM	CHEMBL4087522
9.52	EC50	0.3	nM	CHEMBL4099556
9.52	EC50	0.3	nM	CHEMBL4075397
9.52	IC50	0.3	nM	CHEMBL5275380
9.52	IC50	0.3	nM	CHEMBL6039938
9.40	EC50	0.4	nM	CHEMBL4072494
9.38	IC50	0.413	nM	CHEMBL1650511
9.30	IC50	0.5	nM	CHEMBL6046186
9.30	IC50	0.5	nM	CHEMBL5761445
9.22	IC50	0.6	nM	CHEMBL3687372
9.22	EC50	0.6	nM	CHEMBL4097005
9.22	IC50	0.6	nM	CHEMBL5940677
9.15	EC50	0.7	nM	CHEMBL4097943
9.15	IC50	0.7	nM	CHEMBL6049162
9.15	IC50	0.7	nM	CHEMBL6039415
9.15	IC50	0.7	nM	CHEMBL5997178
9.15	IC50	0.7	nM	CHEMBL5836053
9.10	IC50	0.8	nM	CHEMBL3687381
9.10	EC50	0.8	nM	CHEMBL4079591
9.10	IC50	0.8	nM	CHEMBL1650511
9.10	IC50	0.8	nM	CHEMBL5941602
9.05	IC50	0.9	nM	ELISMETREP
9.05	IC50	0.9	nM	CHEMBL3687404
9.05	IC50	0.9	nM	CHEMBL5833062
9.02	IC50	0.96	nM	CHEMBL3353600
9.00	IC50	1	nM	CHEMBL3687353
9.00	IC50	1	nM	CHEMBL3687380
9.00	IC50	1	nM	CHEMBL6006060
9.00	IC50	1	nM	CHEMBL5794718
9.00	IC50	1	nM	CHEMBL5740070
8.96	IC50	1.1	nM	CHEMBL3687356
8.96	EC50	1.1	nM	CHEMBL4060261
8.96	IC50	1.1	nM	CHEMBL2324349
8.96	IC50	1.1	nM	CHEMBL5809570
8.96	IC50	1.1	nM	CHEMBL5892176
8.96	IC50	1.1	nM	CHEMBL5925916
8.96	IC50	1.1	nM	CHEMBL5755420
8.96	IC50	1.1	nM	CHEMBL5819079
8.96	IC50	1.1	nM	CHEMBL5807187
8.92	IC50	1.2	nM	CHEMBL3687357
8.92	IC50	1.2	nM	CHEMBL6055674
8.89	IC50	1.3	nM	CHEMBL3682568
8.89	IC50	1.3	nM	CHEMBL3687365
8.85	IC50	1.4	nM	CHEMBL3687373
8.85	IC50	1.4	nM	CHEMBL3974529
8.85	EC50	1.4	nM	CHEMBL4105385
8.85	IC50	1.4	nM	CHEMBL5924013
8.85	IC50	1.4	nM	CHEMBL5950176
8.82	IC50	1.5	nM	CHEMBL3687374

PubChem BioAssay actives

452 with measured affinity, of 879 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-ethyl-2-(4-methylphenoxy)-N-(1H-pyrazol-4-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	<0.0001	uM
1-ethyl-3-(4-methylphenoxy)-4-thiophen-2-ylazetidin-2-one	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	<0.0001	uM
(E)-3-(4-methylphenyl)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)prop-2-enamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	<0.0001	uM
(E)-3-(1,3-benzodioxol-5-yl)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)prop-2-enamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	<0.0001	uM
2-(2,3-dihydro-1H-inden-5-yloxy)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	<0.0001	uM
1-(2-aminoethyl)-1-[(3-methoxy-4-phenylmethoxyphenyl)methyl]-3-(1-phenylethyl)urea	1949594: Antagonist activity at human TRPM8 expressed in HEK293 cells	ic50	0.0001	uM
2-(4-methylphenoxy)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0002	uM
N-(4-cyclopropylisoquinolin-3-yl)-4-(2H-tetrazol-5-yl)-N-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide	1949593: Antagonist activity at TRPM8 (unknown origin)	ic50	0.0003	uM
2-(4-methylphenoxy)-N-(1,3-oxazol-2-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0003	uM
N-(3,5-dimethyl-1H-pyrazol-4-yl)-2-(4-methylphenoxy)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0003	uM
3-[4-(trifluoromethyl)-6-[2-(trifluoromethyl)phenyl]-1H-benzimidazol-2-yl]-1-oxa-2-azaspiro[4.5]dec-2-ene	554382: Inhibition of human TRPM8 expressed in HEK293 cells assessed as inhibition of cold-induced channel current by whole cell electrophysiology	ic50	0.0004	uM
2-(4-methylphenoxy)-N-(5-methyl-1H-pyrazol-4-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0004	uM
2-(1,3-benzodioxol-5-yloxy)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0006	uM
(E)-3-(1,3-benzodioxol-5-yl)-N-ethyl-N-(thiophen-2-ylmethyl)prop-2-enamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0007	uM
2-(2,3-dihydro-1H-inden-5-yloxy)-N-ethyl-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0008	uM
4-[(4-tert-butylphenyl)methyl-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0010	uM
5-methoxy-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)-1-benzofuran-2-carboxamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0011	uM
4-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl-(3-methyl-1-benzothiophen-2-yl)sulfamoyl]benzoic acid	1949581: Agonist activity at human TRMP8 expressed in HEK293 cells measured after 24 hrs of menthol activation by patch clamp assay	ic50	0.0011	uM
2-(4-methylphenoxy)-N-(1H-pyrazol-4-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0014	uM
(E)-N-ethyl-3-(4-methylphenyl)-N-(thiophen-2-ylmethyl)prop-2-enamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0020	uM
2-(4-methylphenoxy)-N-(1,2-oxazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0020	uM
4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-[[4-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl]methyl]sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0033	uM
2-(5-tert-butyl-4-chloro-2-methylpyrazol-3-yl)-6-(2-chlorophenyl)-4-methoxy-1H-imidazo[4,5-c]pyridine	1949591: Antagonist activity at human TRMP8 incubated for 24 hrs	ic50	0.0035	uM
2-(4-methoxyphenoxy)-N-(1H-pyrazol-5-yl)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0037	uM
N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(thiophen-2-ylmethyl)benzamide	726253: Inhibition of TRPM8 (unknown origin)	ic50	0.0040	uM
N-[(4S)-4-[4-(trifluoromethoxy)phenyl]-2,3-dihydropyrano[3,2-b]pyridin-4-yl]-3H-benzimidazole-5-carboxamide	1949569: Antagonist activity at human TRPM8 expressed in CHO cells	ic50	0.0040	uM
(10R,15S)-10-(4-chlorophenyl)-13-[(4-fluorophenyl)methyl]-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1665993: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method	ic50	0.0041	uM
[4-hydroxy-2-(2-hydroxyphenyl)-1,3-thiazol-5-yl]-(1,2-oxazolidin-2-yl)methanone	1961441: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in icilin induced Ca2+ efflux preincubated for 5 mins followed by icilin addition and measured for 3 mins by FLIPR assay	ic50	0.0045	uM
(NZ)-N-[1-ethyl-3-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl]-5-(trifluoromethyl)benzimidazol-2-ylidene]benzenesulfonamide	1949591: Antagonist activity at human TRMP8 incubated for 24 hrs	ic50	0.0050	uM
N-[(S)-(3-fluoro-2-pyridinyl)-[3-fluoro-4-(trifluoromethyl)phenyl]methyl]-6-oxo-1H-pyridine-3-carboxamide	1400092: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced intracellular calcium levels preincubated for 2.5 mins followed by icilin addition by CCD-camera-based FLASH luminometric analysis	ic50	0.0050	uM
N-(1-ethyl-5-fluorobenzimidazol-2-yl)-N-[[4-(trifluoromethyl)phenyl]methyl]benzenesulfonamide	1949591: Antagonist activity at human TRMP8 incubated for 24 hrs	ic50	0.0060	uM
6-oxo-N-[(S)-[4-(trifluoromethyl)phenyl]-[3-(trifluoromethyl)-2-pyridinyl]methyl]-1H-pyridine-3-carboxamide	1400092: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced intracellular calcium levels preincubated for 2.5 mins followed by icilin addition by CCD-camera-based FLASH luminometric analysis	ic50	0.0060	uM
4-[[3-fluoro-4-(trifluoromethyl)phenyl]methyl-(3-methyl-1-benzothiophen-2-yl)sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0062	uM
(5R,8S)-5-benzyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	1665993: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method	ic50	0.0066	uM
(10S,15S)-10-(4-fluorophenyl)-13-[3-(trifluoromethyl)phenyl]-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1665993: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method	ic50	0.0077	uM
4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-[[4-(1-methylcyclopropyl)phenyl]methyl]sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0080	uM
N-ethyl-2-(2-hydroxy-4-methylphenoxy)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0080	uM
N-cyclopropyl-2-(4-methylphenoxy)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0080	uM
N-ethyl-2-(4-methylphenoxy)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0080	uM
4-hydroxy-N-[(S)-[4-(trifluoromethyl)phenyl]-[3-(trifluoromethyl)-2-pyridinyl]methyl]benzamide	1400092: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced intracellular calcium levels preincubated for 2.5 mins followed by icilin addition by CCD-camera-based FLASH luminometric analysis	ic50	0.0080	uM
4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-[[4-(trifluoromethoxy)phenyl]methyl]sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0083	uM
1-[2-(3-fluorophenyl)-4-hydroxy-1,3-thiazol-5-yl]propan-1-one	1961442: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in cold stimulated Ca2+ efflux preincubated for 5 mins followed by cold stimulation and measured for 3 mins	ic50	0.0085	uM
(4R)-8-chloro-4-hydroxy-N-[4-(trifluoromethoxy)phenyl]spiro[3,4-dihydrochromene-2,4’-piperidine]-1’-carboxamide	779510: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced 45Ca2+ uptake incubated for 10 mins prior to icilin-challenge measured after 4 mins by liquid scintillation counting analysis	ic50	0.0089	uM
4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-[[4-(trifluoromethyl)phenyl]methyl]sulfamoyl]benzoic acid	1173568: Antagonist activity at human TRPM8 expressed in HEK293 cells assessed as inhibition of menthol induced Ca2+ influx	ic50	0.0089	uM
3-bromo-2-[(1S)-1-di(propan-2-yloxy)phosphoryl-2-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl]-1-benzothiophene	1949580: Agonist activity at human TRMP8 expressed in HEK293 cells incubated for 24 hrs by HTS assay	ic50	0.0090	uM
N-[(S)-(3-fluoro-2-pyridinyl)-[3-fluoro-4-(trifluoromethoxy)phenyl]methyl]-6-oxo-1H-pyridine-3-carboxamide	1400092: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced intracellular calcium levels preincubated for 2.5 mins followed by icilin addition by CCD-camera-based FLASH luminometric analysis	ic50	0.0090	uM
(4R)-8-fluoro-4-hydroxy-N-[4-(trifluoromethoxy)phenyl]spiro[3,4-dihydrochromene-2,4’-piperidine]-1’-carboxamide	779510: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced 45Ca2+ uptake incubated for 10 mins prior to icilin-challenge measured after 4 mins by liquid scintillation counting analysis	ic50	0.0095	uM
5-(2-ethyltetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol-4-ol	1949571: Antagonist activity at cold activated human TRPM8 expressed in HEK293 cells	ic50	0.0100	uM
N-methoxy-2-(4-methylphenoxy)-N-(thiophen-2-ylmethyl)acetamide	1487267: Agonist activity at human TRPM8 expressed in HEK293 cells assessed as increase in intracellular calcium level after 15 mins by Fluo-3-AM dye-based fluorescence assay	ec50	0.0100	uM
N-[(S)-(3-fluoro-2-pyridinyl)-[4-(trifluoromethyl)phenyl]methyl]-6-oxo-1H-pyridine-3-carboxamide	1400092: Antagonist activity at human TRPM8 expressed in CHO cells assessed as inhibition of icilin-induced intracellular calcium levels preincubated for 2.5 mins followed by icilin addition by CCD-camera-based FLASH luminometric analysis	ic50	0.0100	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Menthol	affects binding, increases activity, increases transport, decreases reaction, increases reaction (+3 more)	9
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
icilin	affects reaction, increases response to substance, increases reaction, increases transport, increases activity (+1 more)	5
Calcium	increases transport, affects binding, decreases reaction, increases activity, increases reaction	5
methylmercuric chloride	decreases expression	2
sodium arsenite	increases expression	2
N-(3-aminopropyl)-2-(((3-methylphenyl) methyl)oxy)-N-(2-thienylmethyl)benzamide hydrochloride salt	affects reaction, decreases reaction, increases activity, decreases activity, increases expression	2
allyl isothiocyanate	increases activity	1
pirinixic acid	affects binding, decreases expression, increases activity	1
cannabidiolic acid	decreases expression	1
trichostatin A	decreases expression, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide	decreases reaction, increases activity, decreases activity	1
dorsomorphin	affects cotreatment, decreases expression	1
N-(4-methoxyphenyl)-4-menthone-3-carboxamide	increases activity	1
enzalutamide	decreases expression	1
bisphenol S	increases methylation	1
Rosiglitazone	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Capsaicin	increases activity	1
Copper	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Phenobarbital	increases expression	1
Praziquantel	decreases reaction, increases activity, decreases response to substance	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1

ChEMBL screening assays

160 unique, capped per target: 148 binding, 12 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1118224	Functional	Antagonist activity at human TRPM8 channel	Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. — J Med Chem
CHEMBL1118250	Binding	Activation of TRPM8 channel	Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C9E8	B’SYS HEK 293T TRPM8	Transformed cell line	Female
CVCL_C9J9	WAe009-A-A	Embryonic stem cell	Female
CVCL_D1UQ	Abcam U-87MG TRPM8 KO	Cancer cell line	Male
CVCL_D1ZH	Abcam A-549 TRPM8 KO	Cancer cell line	Male
CVCL_D2DH	Abcam HCT 116 TRPM8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.