RMC-6236

编号: 25074

Cas号: 2765081-21-6

纯度: 98% Min.

Daraxonrasib, also known as RMC-6236 and RAS-IN-2, is a potent and selective RAS(ON) inhibitor. RMC-6236 exhibits potent in vitro activity against RAS-driven cancer cell lines, particularly those harboring KRAS mutations at codon 12. In biochemical assays, RMC-6236 demonstrated low nanomolar EC₅₀ values for inhibiting the interaction between RAS-GTP and RAF, indicating strong binding affinity to both wild-type and mutant RAS proteins. In cellular assays, RMC-6236 effectively inhibited the viability of KRAS G12D-mutant pancreatic cancer cell lines, such as HPAC and Capan-2, with EC₅₀ values of 1.2 and 1.4 nmol/L, respectively. Treatment with RMC-6236 led to sustained suppression of downstream RAS signaling pathways, as evidenced by reduced phosphorylation of ERK (pERK) and S6 (pS6) proteins, and induced apoptosis in these cell lines. Furthermore, a comprehensive screening across 845 cancer cell lines revealed that those with KRAS G12X mutations were significantly more sensitive to RMC-6236, with a median EC₅₀ of 8 nmol/L, compared to cell lines with other oncogenic KRAS mutations.

仅供研究使用。我们不向患者出售。

化学信息

名称	RMC-6236
Iupac 化学名称	(1S,2S)-N-((63S,4S,Z)-11-ethyl-12-(2-((S)-1-methoxyethyl)-5-(4-methylpiperazin-1-yl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-thiazola-1(5,3)-indola-6(1,3)-pyridazinacycloundecaphane-4-yl)-2-methylcyclopropane-1-carboxamide
同义词	RMC-6236; RMC 6236; RMC6236; RAS-IN-2; RAS In 2; daraxonrasib;
英文同义词	RMC-6236; RMC 6236; RMC6236; RAS-IN-2; RAS In 2; daraxonrasib;
分子式	C44H58N8O5S
分子量	811.06
Smile	CC(COC([C@H]1NN(C([C@H](CC2=NC3=CS2)NC([C@H]4C[C@@H]4C)=O)=O)CCC1)=O)(C)CC5=[C@@](N(CC)C6=C5C=C3C=C6)[C@@]7=C([C@H](C)OC)N=CC(N8CCN(C)CC8)=C7
InChiKey
InChi
Cas号	2765081-21-6
相关CAS号

订购信息

包装	价格	库存	纯度	备货期
大货		询价	询价	询价

Request Bulk Quote Download MSDS 电话 : +86-177 0271 9238 Email : sales@sun-shinechem.com

外观性状	类白色固体
纯度	98% Min.
存储	0-4℃，可保存几天到几周；-20℃，可保存几个月。
可溶性	溶于DMSO等有机溶剂
处理方式
运输条件	可以在室温下进行运输。
海关编码

Coming soon.

Targets
Mechanism
Cell study
Animal study
Clinical study

1: Mahadevan KK, Maldonado AS, Li B, Bickert AA, Perdyan A, Kumbhar SV, Piya S, Sockwell A, Morse SJ, Arian K, Sugimoto H, Shalapour S, Hong DS, Heffernan TP, Maitra A, Kalluri R. Inhibitors of oncogenic Kras specifically prime CTLA4 blockade to transcriptionally reprogram Tregs and overcome resistance to suppress pancreas cancer. bioRxiv [Preprint]. 2025 Mar 4:2025.02.28.640711. doi: 10.1101/2025.02.28.640711. PMID: 40093186; PMCID: PMC11908235.

2: Orlen MI, Vostrejs WP, Sor R, McDevitt JC, Kemp SB, Kim IK, Kramer AB, Tovbis Shifrin N, Markosyan N, Clendenin C, Singh M, Quintana E, Menard M, Vonderheide RH, Stanger BZ. T-cell dependency of tumor regressions and complete responses with RAS(ON) multi-selective inhibition in preclinical models of PDAC. Cancer Discov. 2025 Mar 7. doi: 10.1158/2159-8290.CD-24-1475. Epub ahead of print. PMID: 40057911.

3: Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 8. doi: 10.1021/acs.jmedchem.4c02314. Epub ahead of print. PMID: 40056080.

4: Sait SF, Tang KH, Angus SP, Brown R, Sun D, Xie X, Iltis C, Lien M, D Socci N, Bale TA, Davis C, Dixon SAH, Zhang C, Wade Clapp D, Neel BG, Parada LF. Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors. Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2407745121. doi: 10.1073/pnas.2407745121. Epub 2024 Dec 30. PMID: 39793045; PMCID: PMC11725864.

5: Filis P, Salgkamis D, Matikas A, Zerdes I. Breakthrough in RAS targeting with pan-RAS(ON) inhibitors RMC-7977 and RMC-6236. Drug Discov Today. 2025 Jan;30(1):104250. doi: 10.1016/j.drudis.2024.104250. Epub 2024 Nov 24. PMID: 39586491.

6: Vanclooster P, Seghers S, Prenen H. State-of-the-art and upcoming trends in RAS-directed therapies in gastrointestinal malignancies. Curr Opin Oncol. 2024 Jul 1;36(4):313-319. doi: 10.1097/CCO.0000000000001042. Epub 2024 Apr 19. PMID: 38726828.

7: Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, Singh M. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Jun 3;14(6):994-1017. doi: 10.1158/2159-8290.CD-24-0027. PMID: 38593348; PMCID: PMC11149917.

8: Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, Patrucco E, Goodhart G, Dilly J, Gindin Y, Dinglasan N, Wang Y, Lai LP, Cai S, Jiang L, Nasholm N, Shifrin N, Blaj C, Shah H, Evans JW, Montazer N, Lai O, Shi J, Ahler E, Quintana E, Chang S, Salvador A, Marquez A, Cregg J, Liu Y, Milin A, Chen A, Ziv TB, Parsons D, Knox JE, Klomp JE, Roth J, Rees M, Ronan M, Cuevas-Navarro A, Hu F, Lito P, Santamaria D, Aguirre AJ, Waters AM, Der CJ, Ambrogio C, Wang Z, Gill AL, Koltun ES, Smith JAM, Wildes D, Singh M. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024 May;629(8013):919-926. doi: 10.1038/s41586-024-07205-6. Epub 2024 Apr 8. PMID: 38589574; PMCID: PMC11111408.

9: Drugging RAS: Moving Beyond KRASG12C. Cancer Discov. 2023 Dec 12;13(12):OF7. doi: 10.1158/2159-8290.CD-ND2023-0010. PMID: 37871268.

化学结构

RMC-6236

化学信息

订购信息

化学结构

快速订购

产品目录