RMC-6236 (Daraxonrasib)

Chemical Name/IUPAC: (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

SMILES Code: CC(COC([C@H][C@H][C@H]4C[C@@H]4C)=O)=O)CCC1)=O)(C)CC5=[C@@][C@@]7=C([C@H](C)OC)N=CC(N8CCN(C)CC8)=C7

References

[1]  Trends Cancer. 2023 Jan;9(1):42-54. doi: 10.1016/j.trecan.2022.10.001. Epub 2022 Oct 28. Precision oncology provides opportunities for targeting KRAS-inhibitor resistance. Martin Sattler 1, Atish Mohanty 2, Prakash Kulkarni 2, Ravi Salgia 3

[2]  Mullard A. The KRAS crowd targets its next cancer mutations. Nat Rev Drug Discov. 2023 Jan 23. doi: 10.1038/d41573-023-00015-x. Epub ahead of print.

[3]  Wang X, Marx MA. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. J Med Chem. 2022 Feb 24;65(4):3123-3133. doi: 10.1021/acs.jmedchem.1c01688. Epub 2021 Dec 10.

Documents

MSDS-RMC-6236

Frequently Asked Questions (FAQ)

• What is the recommended RMC-6236 solubility and laboratory handling protocol?

  A: RMC-6236 (daraxonrasib) is highly soluble in anhydrous DMSO. According to the material safety data sheet (MSDS), this compound is supplied as a dry solid powder and exhibits a high dust explosion potential if electrostatic charges accumulate. To optimize RMC-6236 solubility / handling research, it is strongly advised to restrict the use of high-resistivity materials such as standard plastics during weighing and formulation. All conductive elements in your analytical system should be properly bonded and grounded. For stock solutions, dissolve the powder in sterile DMSO and divide into single-use aliquots where appropriate. Users should establish storage conditions for prepared solutions according to their own validation requirements and experimental protocols.

• How does RMC-6236 function as a tri-complex inhibitor or RAS molecular glue?

  A: Traditional RAS pathway inhibitors often fail because they only target inactive GDP-bound states or specific single mutations. RMC-6236 is a first-in-class tri-complex inhibitor / RAS molecular glue that targets the active, GTP-bound state of the protein. Upon introduction into a cellular environment, RMC-6236 binds to an abundant intracellular chaperone protein called cyclophilin A (CypA). This initial binding forms a distinct binary complex, which then steric-hinders and locks onto active RAS to create a high-affinity tri-complex. This unique multi-selective mechanism shuts down constitutive downstream oncogenic signaling, making it a critical RAS(ON) multi-selective inhibitor tool compound for modern oncology laboratories.

• Which mutant variants can be evaluated using this pan-RAS (ON) inhibitor research compound?

  A: As a potent pan-RAS inhibitor (research compound), RMC-6236 serves as an excellent benchmark for expanding targeting capabilities beyond traditional G12C restrictions. It is heavily utilized as a RAS(ON) inhibitor to map signaling profiles across a wide spectrum of non-G12C alterations. This makes it a valuable research tool for studying active-state KRAS variants, including G12D, G12V, and related mutations, while evaluating inhibitory profiles across multiple major RAS-driven signaling pathways.

• What is the official regulatory status of Biofargo's RMC-6236 material?

  A: This product is supplied strictly For Research Use Only (RUO). Biofargo provides this molecule exclusively as a laboratory tool compound for in vitro mechanistic exploration, enzymatic assays, and tumor cell line profiling. We do not permit or imply any therapeutic or diagnostic claims anywhere regarding our material. While clinical data in literature—such as the originator's RASolute 302 trial for daraxonrasib—demonstrates the biological relevance of the target pathway, Biofargo’s reagent is not intended for human or animal clinical trials, direct patient treatment, or any in vivo diagnostic use.