XL518
- CAS No.
- 934660-93-2
- Chemical Name:
- XL518
- Synonyms
- CobiMetinib;GDC-0973;XL518;RG7420;CS-1977;Cobimetinib-D4;GDC-0973/RG7420;XL518 ,GDC-0973;XL518 USP/EP/BP;GDC-0973(XL-518)
- CBNumber:
- CB32551361
- Molecular Formula:
- C21H21F3IN3O2
- Molecular Weight:
- 531.31
- MOL File:
- 934660-93-2.mol
- Modify Date:
- 2024/5/21 14:56:49
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Signal word | Warning | |||||||||
| HS Code | 29333990 | |||||||||
| NFPA 704 |
|
XL518 Chemical Properties,Uses,Production
Description
Cobimetinib, codeveloped by Genentech and Exelixis, was approved in August 2015 in Switzerland and November 2015 in the U.S. and Europe for the treatment of unresectable or metastatic BRAFV600 mutationpositive melanoma when used in combination with vemurafenib. Cobimetinib is a potent, highly selective reversible inhibitor of mitogen-activated protein kinases (MEK) 1 and 2,120 which serves to inhibit phosphorylation of ERK1/2,121 disrupting the MAPK pathway which is responsible for cell proliferation, cell survival, and migration.122 Combination of cobimetinib with vemurafenib, an important BRAF inhibitor,123 enables targeting of multiple points on the MAPK pathway, leading to overall enhanced tumor cell apoptosis and response as compared to stand-alone treatment with vemurafenib.124 Specifically, in a representative trial of previously untreated patients with BRAFV600 mutation-positive, unresectable, stage IIIc or IV melanoma, combination of these two therapies led to a significantly improved progression-free survival and overall response rate versus patients treated only with vemurafenib.
Uses
A potent, selective, orally bioavailable inhibitor of MEK1, a component of the RAS/RAF/MEK/ERK pathway. It inhibits proliferation and stimulates apoptosis in a variety of human tumor cell lines. In preclinical xenograft models, oral administration of XL518 results in sustained inhibition of pERK in tumor tissue, but not brain tissue, leading to tumor growth inhibition and regression at well tolerated doses.
brand name
Cotellic
General Description
Class: dual threonine/tyrosine kinase; Treatment: melanoma with BRAF mutations; Other name: GDC-0973, XL518; Oral bioavailability = 46%; Elimination half-life = 44 h; Protein binding = 95%
Pharmacokinetics
Cobimetinib has only moderate oral
bioavailability (46%), likely due to metabolism rather
than incomplete absorption. However, it displays
prolonged elimination half-life (44 h), which supports
a once-daily dosing regimen (60 mg). Following oral administration, the unchanged
cobimetinib and metabolite 4 were the major
circulating components in the plasma up to 48 hours
post dose (AUC0–48), accounting for 21% and 18% of
all the circulating drug-related components,
respectively (Fig. 4).
target
Primary target: MEK1/2
XL518 Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| A.J Chemicals | 91-9810153283 | New Delhi, India | 6124 | 58 | Inquiry |
| CLEARSYNTH LABS LTD. | +91-22-45045900 | Hyderabad, India | 6351 | 58 | Inquiry |
| Pharma Affiliates | 172-5066494 | Haryana, India | 6761 | 58 | Inquiry |
| SynZeal Research Pvt Ltd | +1 226-802-2078 | Gujarat, India | 6522 | 58 | Inquiry |
| Pharmaffiliates Analytics and Synthetics P. Ltd | +91-172-5066494 | Haryana, India | 6773 | 58 | Inquiry |
| Hangzhou FandaChem Co.,Ltd. | 008657128800458; +8615858145714 | China | 9337 | 55 | Inquiry |
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | China | 32836 | 60 | Inquiry |
| career henan chemical co | +86-0371-86658258 +8613203830695 | China | 29888 | 58 | Inquiry |
| BOC Sciences | +1-631-485-4226 | United States | 19553 | 58 | Inquiry |
| Chongqing Chemdad Co., Ltd | +86-023-6139-8061 +86-86-13650506873 | China | 39916 | 58 | Inquiry |