This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Adagrasib is an experimental KRAS inhibitor being investigated for the treatment of KRAS G12C mutant lung and colon adenocarcinomas.

Generic Name
Adagrasib
DrugBank Accession Number
DB15568
Background

Adagrasib (MRTX849) is a KRAS inhibitor developed by Mirati and is currently undergoing trials for KRAS G12C mutant cancers. This mutation makes up >50% of all KRAS mutations.2

The drug AMG-510 is also currently being developed and has the same target.1

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available
External IDs
  • MRTX-849
  • MRTX849

Pharmacology

Indication

MRTX849 is an experimental KRAS inhibitor being investigated for the treatment of KRAS G12C mutant lung and colon adenocarcinomas.2

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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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.2 KRAS G12C mutations impair hydrolysis of GTP, leaving it in the active form.2

MRTX849 inhibits KRAS in these types of cancers.2 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

TargetActionsOrganism
AGTPase KRas
inhibitor
Humans
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
Adverseeffects
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Toxicity

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
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
8EOO6HQF8Y
CAS number
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
Wikipedia
Adagrasib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentAdvanced Colorectal Cancer / Metastatic Colorectal Cancer (CRC)1
3RecruitingTreatmentAdvanced Non Small Cell Lung Cancer (NSCLC) / Metastatic Non-Small Cell Lung Cancer1
2RecruitingTreatmentAdvanced Non Small Cell Lung Cancer (NSCLC) / Metastatic Non-Small Cell Lung Cancer1
1RecruitingTreatmentCancer, Advanced / Malignant Neoplasm of Colon / Malignant Neoplasm of Lung / Malignant Neoplastic Disease / Metastatic Cancers1
1RecruitingTreatmentSolid Tumors, Advanced Solid Tumors1
1, 2Active Not RecruitingTreatmentCancer, Advanced / Malignant Neoplastic Disease / Metastatic Cancers1
1, 2RecruitingTreatmentCancer, Advanced / Malignant Neoplastic Disease / Metastatic Cancers1
Not AvailableAvailableNot AvailableCancer, Advanced / Metastatic Cancers / Neoplasms, Malignant1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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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
  1. 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. [Article]

Drug created at November 01, 2019 18:31 / Updated at November 08, 2021 03:40