| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Sotorasib (AMG-510; AMG510; Lumakras; Lumykras) is a novel, first-in-class and covalent/irreversible inhibitor of KRAS G12C that has been approved by FDA on 5/28/2021 to treat non-small-cell lung cancer (NSCLC). It specifically targets the most common mutation among the three subtypes of Ras proteins (KRas, NRas, and HRas), the KRAS G12C mutation. KRAS gene mutations (e.g. G12C, G12V, G12D, and G13D) are present in approximately 30% of human cancers, and are most common in pancreatic cancer, lung adenocarcinoma, colorectal cancer, gall bladder cancer, thyroid cancer, and bile duct cancer. About 25% of NSCLC patients also have KRAS mutations, and some research suggests that these mutations are associated with a poorer prognosis for NSCLC patients. It has recently been discovered that V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations confer resistance to epidermal growth factor receptor (EGFR) targeted therapies in colorectal cancer; as such, knowledge of the KRAS mutational status can be crucial before TKI therapy is prescribed. All things considered, patients diagnosed with lung adenocarcinoma, colorectal cancer, or pancreatic cancer require novel medical interventions; this is particularly true for those whose cancers are marked by a KRAS mutation, as well as those who have advanced following chemotherapy.
| Targets |
KRAS(G12C)
|
|---|---|
| ln Vitro |
AMG 510 had little effect on KRAS (C118A) but inhibits the nucleotide exchange of recombinant mutant KRAS (G12C/C118A) when catalyzed by SOS1. Additionally, AMG 510 specifically reduces the viability of KRAS p.G12C mutant lines while having no effect on cell lines harboring other KRAS mutations[1].
|
| ln Vivo |
AMG 510 quickly and irreversibly binds to KRAS (G12C) in preclinical tumor models, resulting in long-lasting inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway. When administered orally (once daily) as a single agent, AMG 510 has the ability to induce tumor regression in KRASG12C cancer-bearing mice models[2].
|
| Cell Assay |
Cell Line: NCI-H358 and MIA PaCa-2 cells
Concentration: 1-10 μM Incubation Time: 72 hours Result: Potently impaired cellular viability in both NCI-H358 and MIA PaCa-2 (IC50≈0.006 μM and 0.009 μM respectively). |
| Animal Protocol |
Female ICR-SCID mice
100 mg/kg o.g. |
| References |
| Molecular Formula |
C30H30F2N6O3
|
|---|---|
| Molecular Weight |
560.5944
|
| Exact Mass |
560.23
|
| Elemental Analysis |
C, 64.28; H, 5.39; F, 6.78; N, 14.99; O, 8.56
|
| CAS # |
2296729-00-3
|
| Related CAS # |
Sotorasib racemate; 2252403-56-6; Sotorasib isomer; Sotorasib-d7; 2296729-66-1; 2387559-45-5
|
| Appearance |
Solid powder
|
| SMILES |
C[C@H]1CN(CCN1C2=NC(=O)N(C3=NC(=C(C=C32)F)C4=C(C=CC=C4F)O)C5=C(C=CN=C5C(C)C)C)C(=O)C=C
|
| InChi Key |
NXQKSXLFSAEQCZ-SFHVURJKSA-N
|
| InChi Code |
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
|
| Chemical Name |
6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-[(2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one
|
| Synonyms |
AMG-510; sotorasib; AMG 510; AMG510; trade names: Lumakras; Lumykras
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 50~100 mg/mL (89.2~178.4 mM)
Ethanol: ~13 mg/mL |
|---|---|
| Solubility (In Vivo) |
5%DMSO+ 40%PEG300+ 5%Tween 80+ 50%ddH2O: 5.0mg/ml (8.92mM) (Please use freshly prepared in vivo formulations for optimal results.)
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7838 mL | 8.9192 mL | 17.8383 mL | |
| 5 mM | 0.3568 mL | 1.7838 mL | 3.5677 mL | |
| 10 mM | 0.1784 mL | 0.8919 mL | 1.7838 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04933695 | Active Recruiting |
Drug: Sotorasib | Non-small Cell Lung Cancer | Amgen | January 28, 2022 | Phase 2 |
| NCT05054725 | Active Recruiting |
Drug: RMC-4630 Drug: Sotorasib |
Non-Small Cell Lung Cancer | Revolution Medicines, Inc. | December 30, 2021 | Phase 2 |
| NCT05198934 | Active Recruiting |
Drug: Sotorasib Drug: Panitumumab Drug: Regorafenib |
Colorectal Cancer (CRC) |
Amgen | April 19, 2022 | Phase 3 |
| NCT05993455 | Active Recruiting |
Drug: Oral sotorasib + IV Panitumumab |
Efficacy | Korea University Anam Hospital |
July 3, 2023 | Phase 2 |
| NCT04303780 | Active Recruiting |
Drug: AMG 510 Drug: Docetaxel |
KRAS p, G12c Mutated / Advanced Metastatic NSCLC |
Amgen | June 4, 2020 | Phase 3 |
|
|---|
AMG 510 inhibits ERK phosphorylation and growth of KRASG12C-mutant tumours in vivo.Nature. 2019 Nov;575(7781):217-223. |
 Clinical activity of AMG 510 in patients with lung cancer in first-in-human dose-escalation study.Nature. 2019 Nov;575(7781):217-223. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
AMG 510 exploits a cryptic groove in KRAS(G12C) to enhance potency and selectivity.