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Dabrafenib

Description Synthetic Methods Biological activity How to use Major Side Effects In vitro In vivo References
Dabrafenib
Dabrafenib structure
CAS No.
1195765-45-7
Chemical Name:
Dabrafenib
Synonyms
CS-658;Dabrafenib;GSK2118436A;Debrafenib API;Dabrafenib Base;Dabrafenib, >=98%;Dabrafenib KB-57246;Debrafenib free base;Dabrafenib USP/EP/BP;Dabrafenib(free base)
CBNumber:
CB32604230
Molecular Formula:
C23H20F3N5O2S2
Formula Weight:
519.56
MOL File:
1195765-45-7.mol

Dabrafenib Properties

Boiling point:
653.7±65.0 °C(Predicted)
Density 
1.443
form 
White solid.
pka
6.62±0.10(Predicted)
FDA UNII
QGP4HA4G1B
ATC code
L01EC02
SAFETY
  • Risk and Safety Statements
HS Code  29350090

Dabrafenib price More Price(41)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 16989 Dabrafenib ≥98% 1195765-45-7 10mg $67 2021-12-16 Buy
Cayman Chemical 16989 Dabrafenib ≥98% 1195765-45-7 5mg $35 2021-12-16 Buy
TRC D101000 Dabrafenib 1195765-45-7 25mg $165 2021-12-16 Buy
ChemScene CS-0692 Dabrafenib 99.97% 1195765-45-7 200mg $190 2021-12-16 Buy
ApexBio Technology B1407 Dabrafenib(GSK2118436) 1195765-45-7 50mg $150 2021-12-16 Buy

Dabrafenib Chemical Properties,Uses,Production

Description

N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide is well known as dabrafenib. It is a drug for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase-I and -II in patients with BRAF(V600)-mutated metastatic melanoma1,2. Its mechanism of action is acted as a Protein Kinase Inhibitor, and Cytochrome P450 3A4 Inducer, and Cytochrome P450 2B6 Inducer, and Cytochrome P450 2C8 Inducer, and Cytochrome P450 2C9 Inducer, and Cytochrome P450 2C19 Inducer, and Organic Anion Transporting Polypeptide 1B1 Inhibitor, and Organic Anion Transporting Polypeptide 1B3 Inhibitor, and Organic Anion Transporter 1 Inhibitor, and Organic Anion Transporter 3 Inhibitor, and Breast Cancer Resistance Protein Inhibitor3,4. It is not indicated for the treatment of patients with wild-type BRAF melanoma or wild-type BRAF NSCLC. MEKINIST is not indicated for the treatment of patients with melanoma who have progressed on prior BRAF-inhibitor therapy5.

Synthetic Methods

The key step in the synthesis of Dabrafenib is the construction of the 1,3-thiazole ring, which is usually carried out by the closing ring directly of thioamide (as a 1,3-binuclear reagent) and anα-carbonyl halide (as a 1,2-amphiphilic reagent). Sulfonyl chloride 1 and aniline 2 gave sulfonamide 3 under basic conditions. Methyl pyrimidine 4 with non-nucleophilic strong alkali LiHMDS pull out the acid proton on the methyl and react with 3 to obtain 5, and the latter has α-bromination with NBS to obtain 1,2-amphiphilic reagent 6, and then 6 reacts with 1 , 3-parent nucleotides 7 to close the ring to obtain 8, and finally reacts with ammonia to obtain Dabrafenib.
synthetic route of Dabrafenib
Figure 1: synthetic route of Dabrafenib

Biological activity

Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with an IC50 of 0.8 nM, and effects for B-Raf (wt) and c-Raf is 4 and 6 fold lower respectively.

How to use

It is usually taken twice a day on an empty stomach, 1 hour before or 2 hours after a meal. Take dabrafenib about 12 hours apart at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Do not stop taking dabrafenib without talking to your doctor.
Swallow the capsules whole; do not split, chew, or crush them.
Your doctor may adjust your dose of dabrafenib depending on your response to treatment and any side effects that you experience. Talk to your doctor about how you are feeling during your treatment.

Major Side Effects

The following side effects are common (occurring in greater than 30%) for patients taking dabrafenib :

These side effects are less common side effects (occurring in about 10-29%) of patients receiving dabrafenib:

In vitro

Dabrafenib is selective for Raf kinases and is 400 times more active against B-Raf than other tested 91% kinases. Dabrafenib inhibits B-RafV600E kinase, resulting in reduced phosphorylation of ERK and inhibition of cell proliferation. The cells stagnate in the G1 phase in cancer cells that specifically encode mutated B-RafV600E.

In vivo

Dabrafenib (oral) inhibits the growth of B-RafV600E mutated melanoma (A375P). Dabrafenib (oral) also inhibits tumor growth, subcutaneously injecting colon cancer (Colo205) in immunocompromised mice.

References

  1. https://www.caymanchem.com/product/16989
  2. https://en.wikipedia.org/wiki/Dabrafenib
  3. https://pubchem.ncbi.nlm.nih.gov/compound/Dabrafenib
  4. Menzies, A. M., and G. V. Long. "Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. " Clinical Cancer Research 20.8(2014): 2035-2043.
  5. https://www.hcp.novartis.com/products/tafinlar-mekinist/

Description

In May 2013, the US FDA approved dabrafenib (also referred to as GSK 2118436) for the treatment of patients with unresectable or metastatic melanoma with the BRAFV600E mutation as detected by a FDA-approved test. Dabrafenib was identified from a screen of an oncology-directed kinase collection, followed by extensive structure–activity relationships (SAR) on an initial thiazole lead. Dabrafenib is a potent inhibitor of B-BRAFV600E kinase (IC50=0.65 nM) compared to its potency against wild-type B-raf (IC50=3.2 nM). It also inhibits other kinases (e.g., CRAF) and other mutant B-raf kinases (BRAFV600E and BRAFV600D) with enzyme IC50s of <5 nM and is fairly selective versus a panel of 270 kinases. Consistent with its in vitro activity, oral administration of dabrafenib inhibits the growth of B-RafV600E mutant melanoma (A375P) and colon cancer (Colo205) human tumor xenografts growing subcutaneously in immunocompromised mice. Key steps in the synthesis of dabrafenib are condensation of an aryl sulfonamide ester with the lithium anion of 2-chloro-4-methylpyrimidine to generate a ketone intermediate and bromination of the ketone intermediate with N-bromosuccinamide followed by cyclization with tert-butyl thioamide to afford the desired thiazole core.

Originator

GlaxoSmithKline (United States)

Uses

Dabrafenib is an inhibitor of mutated BRAF kinase and has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.

Definition

ChEBI: An organofluorine compound and antineoplastic agent, used as its mesylate salt in treatment of metastatic melanoma.

brand name

Tafinlar

Dabrafenib synthesis

1195768-23-0
1195765-45-7
Synthesis of Dabrafenib from N-{3-[5-(2-chloro-4-pyriMidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl]-2-fluoraphenyl}-2,6-difluorobenzenesulfonaMide

Dabrafenib Preparation Products And Raw materials

Raw materials

Preparation Products


Dabrafenib Suppliers

Global( 205)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Henan DaKen Chemical CO.,LTD.
+86-371-66670886
info@dakenchem.com China 15427 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26782 60
career henan chemical co
+86-0371-55982848
sales@coreychem.com China 29954 58
Zhejiang ZETian Fine Chemicals Co. LTD
18957127338
stella@zetchem.com China 2008 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28229 58
BOC Sciences
1-631-485-4226
1-631-614-7828 inquiry@bocsci.com United States 19752 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58
Jurong Coupling Biotechnology Co., Ltd.
13656108824
coupling278191416@hotmail.com CHINA 184 58
Zhuozhou Wenxi import and Export Co., Ltd
+8613111626072 (WhatsApp)
Wechat: +8613111626072 Wickr me: waynehu zzwenxi@126.com CHINA 13187 58

View Lastest Price from Dabrafenib manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-10-20 Dabrafenib
1195765-45-7
US $95.00-79.00 / KG 1KG 99% 9000kg/per week Hebei Lingding Biological Technology Co., Ltd
2021-07-13 Dabrafenib
1195765-45-7
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
2021-07-10 Dabrafenib
1195765-45-7
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd

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