AMG-510
Identification
- Name
- AMG-510
- Accession Number
- DB15569
- Description
AMG-510 is an acrylamide derived KRAS inhibitor developed by Amgen and is currently undergoing clinical trials for solid tumors with KRAS G12C mutations.1,3 This mutation makes up >50% of all KRAS mutations.2 It is the first experimental KRAS inhibitor.1
The drug MRTX849 is also currently being developed and has the same target.1
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 560.606
Monoisotopic: 560.234745176 - Chemical Formula
- C30H30F2N6O3
- Synonyms
- Kras G12C inhibitor 9
- External IDs
- AMG 510
- AMG-510
- AMG510
Pharmacology
- Indication
AMG-510 is being investigated for the treatment of KRAS G12C mutant non small cell lung cancer, colorectal cancer, and appendix cancer.1
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
- Not Available
- Mechanism of action
Normally GTP binds to KRAS, activating the protein and promoting effectors to the MAP kinase pathway.3 GTP is hydrolyzed to GDP, and KRAS is inactivated.4 KRAS G12C mutations impair hydrolysis of GTP, leaving it in the active form.4
AMG-510 binds to the cysteine residue in KRAS G12C mutations, holding the protein in its inactive form.1 This mutation is present in 13% of non small cell lung cancer, 3% of colorectal and appendix cancer, and 1-3% of solid tumors.1
Target Actions Organism AGTPase KRas inhibitorHumans - Absorption
- Not Available
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half-life
- Not Available
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
- Not Available
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Not Available
- Classification
- Not classified
Chemical Identifiers
- UNII
- 2B2VM6UC8G
- CAS number
- 2252403-56-6
- InChI Key
- NXQKSXLFSAEQCZ-SFHVURJKSA-N
- InChI
- InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
- IUPAC Name
- 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-[4-methyl-2-(propan-2-yl)pyridin-3-yl]-4-[(2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl]-1H,2H-pyrido[2,3-d]pyrimidin-2-one
- SMILES
- CC(C)C1=NC=CC(C)=C1N1C(=O)N=C(N2CCN(C[C@@H]2C)C(=O)C=C)C2=CC(F)=C(N=C12)C1=C(O)C=CC=C1F
References
- General References
- Authors unspecified: AMG 510 First to Inhibit "Undruggable" KRAS. Cancer Discov. 2019 Aug;9(8):988-989. doi: 10.1158/2159-8290.CD-NB2019-073. Epub 2019 Jun 12. [PubMed:31189530]
- Fiala O, Pesek M, Finek J, Benesova L, Belsanova B, Minarik M: The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Cancer Genet. 2013 Jan-Feb;206(1-2):26-31. doi: 10.1016/j.cancergen.2012.12.003. Epub 2013 Jan 10. [PubMed:23313110]
- Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR: The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Oct 30. pii: 10.1038/s41586-019-1694-1. doi: 10.1038/s41586-019-1694-1. [PubMed:31666701]
- Christensen JG, Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, Sudhakar N, Bowcut V, Baer BR, Ballard JA, Burkard MR, Fell JB, Fischer JP, Vigers GP, Xue JY, Gatto S, Fernandez-Banet J, Pavlicek A, Velastegui K, Chao RC, Barton J, Pierobon M, Baldelli E, Patricoin EF, Cassidy DP, Marx MA, Rybkin II, Johnson ML, Ou SI, Lito P, Papadopoulos KP, Janne PA, Olson P: The KRASG12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients. Cancer Discov. 2019 Oct 28. pii: 2159-8290.CD-19-1167. doi: 10.1158/2159-8290.CD-19-1167. [PubMed:31658955]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Recruiting Treatment KRAS p, G12c Mutated /Advanced Metastatic NSCLC 1 2 Not Yet Recruiting Treatment Adenocarcinoma of the Lung / Non-Small Cell Lung Carcinoma (NSCLC) / Recurrent Lung Non-Squamous Non-Small Cell Carcinoma / Stage IV Lung Cancer AJCC v8 / Stage IVA Lung Cancer AJCC v8 / Stage IVB Lung Cancer AJCC v8 1 1 Recruiting Treatment Advanced/Metastatic Solid Tumors With KRAS p.G12C Mutation 1 1, 2 Recruiting Treatment KRAS p.G12C Mutant Advanced Solid Tumors 1 Not Available Available Not Available Locally Advanced Metastatic NSCLC / Locally Advanced Unresectable NSCLC / Non-Small Cell Lung Carcinoma (NSCLC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0185 mg/mL ALOGPS logP 3.6 ALOGPS logP 4.74 ChemAxon logS -4.5 ALOGPS pKa (Strongest Acidic) 6.98 ChemAxon pKa (Strongest Basic) 4.74 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 102.23 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 150.12 m3·mol-1 ChemAxon Polarizability 57.21 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein complex binding
- Specific Function
- Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838).
- Gene Name
- KRAS
- Uniprot ID
- P01116
- Uniprot Name
- GTPase KRas
- Molecular Weight
- 21655.67 Da
References
- Authors unspecified: AMG 510 First to Inhibit "Undruggable" KRAS. Cancer Discov. 2019 Aug;9(8):988-989. doi: 10.1158/2159-8290.CD-NB2019-073. Epub 2019 Jun 12. [PubMed:31189530]
- Fiala O, Pesek M, Finek J, Benesova L, Belsanova B, Minarik M: The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Cancer Genet. 2013 Jan-Feb;206(1-2):26-31. doi: 10.1016/j.cancergen.2012.12.003. Epub 2013 Jan 10. [PubMed:23313110]
- Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR: The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Oct 30. pii: 10.1038/s41586-019-1694-1. doi: 10.1038/s41586-019-1694-1. [PubMed:31666701]
Drug created on November 01, 2019 12:34 / Updated on June 12, 2020 10:53