A3004-500mg | Vemurafenib (PLX4032, RG7204) [918504-65-1] Clinisciences

Vemurafenib is an inhibitor of BRAF kinase. It inhibits BRAF^V600E and also has inhibitory activity in vitro against several other kinds of kinases, including CRAF, ARAF and wild-type BRAF. Vemurafenib is a competitive small-molecule serine–threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Vemurafenib can also give rise to activation of downstream MEK by normal RAF homo- and heterodimers in non-BRAF mutated cells, which has been shown to be caused by transactivation of the nondrug-bound partner in BRAF to CRAF heterodimers and CRAF to CRAF homodimers.

Reference

Keith. T Flaherty, Uma Yasothan and Peter Kirkpatrick. Vemurafenib. Nature Reviews Drug Discovery. 2011; 10: 811-812.

Jason J. Luke, F. Stephen Hodi. Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma. Clinical Cancer Research. 2012; 18: 9-14.

1. Ali Talebi, Vincent de Laat, et al. "Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy." J Exp Clin Cancer Res. 2023 Apr 19;42(1):92. PMID: 37072838
2. MENGTING OU, XICHAO XU, et al. "MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3." Oncol Rep. 2021 Jul;46(1):120. PMID:33955525
3. Satoh TK, Mellett M, et al. "IL-36γ drives skin toxicity induced by EGFR/MEK inhibition and commensal Cutibacterium acnes." J Clin Invest. 2019 Dec 5. pii: 128678. PMID:31805013
4. Sechi M, Lall RK, et al. "Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling:insights from in vitro and in vivo melanoma models." Sci Rep. 2018 Oct 24;8(1):15726. PMID:30356079
5. Zanconato F, Battilana G, et al. "Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4." Nat Med. 2018 Oct;24(10):1599-1610. PMID:30224758
6. Hwang BJ, Adhikary G, et al. "Chk1 inhibition as a novel therapeutic strategy in melanoma." Oncotarget. 2018 Jul 13;9(54):30450-30464. PMID:30100999
7. Talebi A, Dehairs J, et al. "Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy." Nat Commun.2018 Jun 27;9(1):2500. PMID:29950559
8. Zuo Q, Liu J, et al. "AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma."Oncogene. 2018 Mar 19. PMID:29551771
9. Fisher ML, Grun D, et al. "Inhibition of YAP function overcomes BRAF inhibitor resistance in melanoma cancer stem cells." Oncotarget.2017 Nov 22;8(66):110257-110272. PMID:29299145
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11. Basu R, Baumgaertel N, et al. "Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps. Horm Cancer." 2017 Jun;8(3):143-156. PMID:28293855
12. Yuan He, Djoke Hendriks, et al. "Melanoma-directed activation of apoptosis using a novel bispecific antibody directed at MCSP and TRAIL receptor 2/Death Receptor 5." Journal of Investigative Dermatology,February 2016, volume 136, pages 541-4.

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Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	489.93
Cas No.	918504-65-1
Formula	C₂₃H₁₈ClF₂N₃O₃S
Synonyms	Vemurafenib, Zelboraf, PLX-4032, RG7204, RO5185426
Solubility	≥24.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Chemical Name	N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide
SDF	Download SDF
Canonical SMILES	CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=NC=C(C=C23)C4=CC=C(C=C4)Cl)F
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment:
Cell lines	MALME-3M melanoma cell lines
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions	24 h; 10 μM
Applications	In melanoma cell lines, RG7204 was a potent inhibitor of proliferation in those expressing BRAFV600E but not BRAFWT. RG7204 also potently inhibited proliferation of melanoma cell lines expressing other codon 600 BRAF mutations (V600D, V600 K, and V600R).
Animal experiment:
Animal models	Athymic nude mice
Dosage form	100 mg/kg bid; oral taken.
Applications	In mice bearing Colo829 tumor xenografts, RG7204 at 100 mg/kg bid for 21 days showed greatly improved antitumor activity compared both with vehicle (P = 0.001) at the end of the study on day 38 after the tumor cell implant. There was complete tumor regression in all 10 mice treated with RG7204 by the end of the study. Survival in the mice treated with RG7204 was significantly better than in those treated with vehicle (P = 0.0008).
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Yang H, Higgins B, Kolinsky K, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models [J]. Cancer research, 2010, 70 (13): 5518-5527.

Description	Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM.
Targets	B-Raf^V600E	C-Raf	MAP4K5 (KHS1)	SRMS	ACK1	FGR
IC50	31 nM	48 nM	51 nM	18 nM	19 nM	63 nM