MRTX849 acid, a derivative of MRTX849, can be used in the synthesis of PROTAC LC-2 (HY-137516). LC-2 is a potent and first-in-class PROTAC capable of degrading endogenous KRAS G12C (DC50s between 0.25 and 0.76 μM).

Product information

CAS Number: 2561529-96-0

Molecular Weight: 662.15

Formula: C34H37ClFN7O4

Chemical Name: 3-[(2S)-2-({[7-(8-chloronaphthalen-1-yl)-4-[(3S)-3-(cyanomethyl)-4-(2-fluoroprop-2-enoyl)piperazin-1-yl]-5H,6H,7H,8H-pyrido[3,4-d]pyrimidin-2-yl]oxy}methyl)pyrrolidin-1-yl]propanoic acid

Smiles: C=C(F)C(=O)N1CCN(C[C@@H]1CC#N)C1N=C(N=C2CN(CCC2=1)C1=CC=CC2C=CC=C(Cl)C=21)OC[C@@H]1CCCN1CCC(O)=O

InChiKey: CWTHNCSWSDACRS-DQEYMECFSA-N

InChi: InChI=1S/C34H37ClFN7O4/c1-22(36)33(46)43-18-17-42(19-24(43)10-13-37)32-26-11-15-41(29-9-3-6-23-5-2-8-27(35)31(23)29)20-28(26)38-34(39-32)47-21-25-7-4-14-40(25)16-12-30(44)45/h2-3,5-6,8-9,24-25H,1,4,7,10-12,14-21H2,(H,44,45)/t24-,25-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 130 mg/mL (196.33 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

LC-2 induces degradation of endogenous KRASG12C in multiple KRAS mutant cancer cell (NCI-H2030, MIA PaCa-2, SW1573, NCI-H23 and NCI-H358 cells) with DC50s between 0.25 and 0.76 μM. LC-2-induced KRASG12C degradation occurs via a bona fide PROTAC mechanism. MIA PaCa-2, NCI-H23, and SW1573 cells are treated with 2.5 μM of LC-2 for 6, 24, 48, and 72 h. In all three cell lines, maximal KRAS degradation occurred within 24 h and was sustained up to 72 h. LC-2-induced (2.5 μM; 6-24 hours) KRAS G12C degradation modulates Erk signaling in homozygous and heterozygous KRAS mutant cell lines.

Products are for research use only. Not for human use.