AMG-333

Drug which acts as a potent and selective blocker of the TRPM8 ion channel

AMG-333
Identifiers

IUPAC name 6-{[(S)-(3-fluoropyridin-2-yl)-[3-fluoro-4-(trifluoromethoxy)phenyl]methyl]carbamoyl}pyridine-3-carboxylic acid
CAS Number	1416799-28-4^Y
PubChem CID	71144018
ChemSpider	72380128
UNII	FR70864511
ChEMBL	ChEMBL4241349
Chemical and physical data
Formula	C₂₀H₁₂F₅N₃O₄
Molar mass	453.325 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1=CC(=C(N=C1)[C@H](C2=CC(=C(C=C2)OC(F)(F)F)F)NC(=O)C3=NC=C(C=C3)C(=O)O)F
InChI InChI=1S/C20H12F5N3O4/c21-12-2-1-7-26-17(12)16(10-4-6-15(13(22)8-10)32-20(23,24)25)28-18(29)14-5-3-11(9-27-14)19(30)31/h1-9,16H,(H,28,29)(H,30,31)/t16-/m0/s1 Key:QEBYISWYMFIXOZ-INIZCTEOSA-N

AMG-333 is a drug which acts as a potent and selective blocker of the TRPM8 ion channel, which is the main receptor responsible for the sensation of cold. It was developed as a potential treatment for migraine.^[1]

References

^ Horne DB, Biswas K, Brown J, Bartberger MD, Clarine J, Davis CD, et al. (September 2018). "Discovery of TRPM8 Antagonist ( S)-6-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic Acid (AMG 333), a Clinical Candidate for the Treatment of Migraine". Journal of Medicinal Chemistry. 61 (18): 8186–8201. doi:10.1021/acs.jmedchem.8b00518. PMID 30148953. S2CID 52095823.

TRP channel modulators

TRPA

Activators	4-Hydroxynonenal 4-Oxo-2-nonenal 4,5-EET 12S-HpETE 15-Deoxy-Δ^12,14-prostaglandin J2 α-Sanshool (ginger, Sichuan and melegueta peppers) Acrolein Allicin (garlic) Allyl isothiocyanate (mustard, radish, horseradish, wasabi) AM404 ASP-7663 Bradykinin Cannabichromene (cannabis) Cannabidiol (cannabis) Cannabigerol (cannabis) Cinnamaldehyde (cinnamon) CR gas (dibenzoxazepine; DBO) CS gas (2-chlorobenzal malononitrile) Cuminaldehyde (cumin) Curcumin (turmeric) Dehydroligustilide (celery) Diallyl disulfide Dicentrine (Lindera spp.) Farnesyl thiosalicylic acid Formalin Gingerols (ginger) Hepoxilin A3 Hepoxilin B3 Hydrogen peroxide Icilin Isothiocyanate JT-010 Ligustilide (celery, Angelica acutiloba) Linalool (Sichuan pepper, thyme) Methylglyoxal Methyl salicylate (wintergreen) N-Methylmaleimide Nicotine (tobacco) Oleocanthal (olive oil) Paclitaxel (Pacific yew) Paracetamol (acetaminophen) PF-4840154 Phenacyl chloride Polygodial (Dorrigo pepper) Shogaols (ginger, Sichuan and melegueta peppers) Tear gases Tetrahydrocannabinol (cannabis) Tetrahydrocannabiorcol Thiopropanal S-oxide (onion) Umbellulone (Umbellularia californica) WIN 55,212-2
Blockers	A-967079 AM-0902 Dehydroligustilide (celery) HC-030031 Nicotine (tobacco) PF-04745637 Ruthenium red

Activators

4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ^12,14-prostaglandin J2
α-Sanshool (ginger, Sichuan and melegueta peppers)
Acrolein
Allicin (garlic)
Allyl isothiocyanate (mustard, radish, horseradish, wasabi)
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis)
Cannabidiol (cannabis)
Cannabigerol (cannabis)
Cinnamaldehyde (cinnamon)
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin)
Curcumin (turmeric)
Dehydroligustilide (celery)
Diallyl disulfide
Dicentrine (Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (ginger)
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (celery, Angelica acutiloba)
Linalool (Sichuan pepper, thyme)
Methylglyoxal
Methyl salicylate (wintergreen)
N-Methylmaleimide
Nicotine (tobacco)
Oleocanthal (olive oil)
Paclitaxel (Pacific yew)
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper)
Shogaols (ginger, Sichuan and melegueta peppers)
Tear gases
Tetrahydrocannabinol (cannabis)
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion)
Umbellulone (Umbellularia californica)
WIN 55,212-2

Blockers

TRPC

Activators	Adhyperforin (St John's wort) Diacyl glycerol GSK1702934A Hyperforin (St John's wort) Substance P
Blockers	DCDPC DHEA-S Flufenamic acid GSK417651A GSK2293017A Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid Niflumic acid Pregnenolone sulfate Progesterone Pyr3 Tolfenamic acid

TRPM

Activators	ADP-ribose BCTC Calcium (intracellular) CIM-0216 Cold Coolact P Cooling Agent 10 Eucalyptol (eucalyptus) Frescolat MGA Frescolat ML Geraniol Hydroxycitronellal Icilin Linalool Menthol (mint) PMD 38 Pregnenolone sulfate Rutamarin (Ruta graveolens) Steviol glycosides (e.g., stevioside) (Stevia rebaudiana) Sweet tastants (e.g., glucose, fructose, sucrose; indirectly) Thio-BCTC WS-12
Blockers	AMG-333 Capsazepine Clotrimazole DCDPC Elismetrep Flufenamic acid Meclofenamic acid Mefenamic acid N-(p-Amylcinnamoyl)anthranilic acid Nicotine (tobacco) Niflumic acid Ononetin PF-05105679 RQ-00203078 Ruthenium red Rutamarin (Ruta graveolens) Tolfenamic acid TPPO TRPM4-IN-5

Activators

ADP-ribose
BCTC
Calcium (intracellular)
CIM-0216
Cold
Coolact P
Cooling Agent 10
Eucalyptol (eucalyptus)
Frescolat MGA
Frescolat ML
Geraniol
Hydroxycitronellal
Icilin
Linalool
Menthol (mint)
PMD 38
Pregnenolone sulfate
Rutamarin (Ruta graveolens)
Steviol glycosides (e.g., stevioside) (Stevia rebaudiana)
Sweet tastants (e.g., glucose, fructose, sucrose; indirectly)
Thio-BCTC
WS-12

Blockers

TRPML

Activators	EVP21 MK6-83 ML-SA1 ML2-SA1 PI(3,5)P₂ SF-22 SN-2
Blockers	ML-SI3 PI(4,5)P₂

TRPP

Activators	Triptolide (Tripterygium wilfordii)
Blockers	Ruthenium red

TRPV

Activators	2-APB 5',6'-EET 9-HODE 9-oxoODE 12S-HETE 12S-HpETE 13-HODE 13-oxoODE 20-HETE α-Sanshool (ginger, Sichuan and melegueta peppers) Allicin (garlic) AM404 Anandamide Bisandrographolide (Andrographis paniculata) Camphor (camphor laurel, rosemary, camphorweed, African blue basil, camphor basil) Cannabidiol (cannabis) Cannabidivarin (cannabis) Capsaicin (chili pepper) Carvacrol (oregano, thyme, pepperwort, wild bergamot, others) DHEA Diacyl glycerol Dihydrocapsaicin (chili pepper) Estradiol Eugenol (basil, clove) Evodiamine (Euodia ruticarpa) Gingerols (ginger) GSK1016790A Heat Hepoxilin A3 Hepoxilin B3 Homocapsaicin (chili pepper) Homodihydrocapsaicin (chili pepper) Incensole (incense) Lysophosphatidic acid Low pH (acidic conditions) Menthol (mint) N-Arachidonoyl dopamine N-Oleoyldopamine N-Oleoylethanolamide Nonivamide (PAVA) (PAVA spray) Nordihydrocapsaicin (chili pepper) Paclitaxel (Pacific yew) Paracetamol (acetaminophen) Phenylacetylrinvanil Phorbol esters (e.g., 4α-PDD) Piperine (black pepper, long pepper) Polygodial (Dorrigo pepper) Probenecid Protons RhTx Rutamarin (Ruta graveolens) Resiniferatoxin (RTX) (Euphorbia resinifera/pooissonii) Shogaols (ginger, Sichuan and melegueta peppers) Tetrahydrocannabivarin (cannabis) Thymol (thyme, oregano) Tinyatoxin (Euphorbia resinifera/pooissonii) Tramadol Vanillin (vanilla) Zucapsaicin
Blockers	α-Spinasterol (Vernonia tweediana) AMG-517 AMG-9810 Asivatrep BCTC Cannabigerol (cannabis) Cannabigerolic acid (cannabis) Cannabigerovarin (cannabis) Cannabinol (cannabis) Capsazepine DCDPC DHEA DHEA-S Flufenamic acid GRC-6211 HC-067047 Lanthanum Mavatrep Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid NGD-8243 Niflumic acid Pregnenolone sulfate RN-1734 RN-9893 Ruthenium red SB-366791 SB-705498 Tivanisiran Tolfenamic acid TRPV3-74a

Activators