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Product FOB Price Min.Order Supply Ability Supplier
Venetoclax
Cas No: 1257044-40-8
No Data 1 Gram 1000 Gram/Week Shanghai BetterBioChem Co., Ltd. Contact Supplier
1257044-40-8/Venetoclax
Cas No: 1257044-40-8
No Data 1 Milligram hundreds of Kilogram/Month Hangzhou JINLAN Pharm-Drugs Technology Co., Ltd Contact Supplier
Venetoclax ABT-199
Cas No: 1257044-40-8
No Data 1 Kilogram 500 Kilogram/Month Huarong Industrial Group Ltd. Contact Supplier
ABT-199 (GDC-0199)Venetoclax
Cas No: 1257044-40-8
No Data 100 Gram 1 Metric Ton/Month Senova Technology Company Limited Contact Supplier
Venetoclax
Cas No: 1257044-40-8
No Data No Data 5 Metric Ton/Day Shanghai Innopharm Industrial Co.,Ltd Contact Supplier
Venetoclax supplier with documents support,CAS NO:1257044-40-8
Cas No: 1257044-40-8
No Data 1 Gram 10kgs Kilogram/Month HANGZHOU FOREWIN PHARMA CO.,LTD. Contact Supplier
Venetoclax supplier in China
Cas No: 1257044-40-8
USD $ 2.0-2.0 / Kilogram 1 Kilogram 1-10 Metric Ton/Month Dayang Chem (Hangzhou) Co.,Ltd. Contact Supplier
Lab supply ABT199, GDC0199, Venetoclax powder for research
Cas No: 1257044-40-8
USD $ 300.0-500.0 / Gram 1 Gram 100 Metric Ton/Year Hubei Vanz Pharm Co.,Ltd Contact Supplier
Safety Delivery ABT-199 CAS 1257044-40-8
Cas No: 1257044-40-8
USD $ 50.0-200.0 / Kilogram 10 Kilogram 1000 Kilogram/Month Hebei Yingong New Material Technology Co.,Ltd . Contact Supplier
Factory Price API 99% ABT-199 1257044-40-8 GMP Manufacturer
Cas No: 1257044-40-8
USD $ 0.1-0.1 / Gram 1 Gram 100 Metric Ton/Year Xi'an Xszo Chem Co., Ltd. Contact Supplier

1257044-40-8 Usage

BCL-2 inhibitor

Venetoclax is a first-in-class, oral, selective BCL-2 inhibitor (BH3-only mimetic). The drug is approved in numerous countries, including those of the EU and in the USA, for the treatment of adults with relapsed or refractory (RR) CLL. The drug arose from research by Abbott Laboratories (now AbbVie) during a collaboration with Genentech and is being codeveloped by AbbVie and Genentech/Roche primarily.

Chemical Synthesis

The manufacturing route to venetoclax takes place by coupling of three key structural subunits: azaindole 162, sulfonamide 165, and piperazine 172. The first of these subunits was generated in two steps from commercially available 4-bromo-2-fluoro-1-iodo-benzene (159). Grignard formation of iodide 159 (i-PrMgCl) followed by quenching with Boc2O provided the desired tert-butyl ester 160 without the need for chromatographic purification. Aromatic substitution of crude 160 with azaindole 161 provided access to 162 in 86% yield after recrystallization from EtOAc/heptane. Sulfonamide 165 was formed in 91% yield and 99.9% purity via aromatic substitution of commercially available 163 with amine 164 at 80 °C (DIPEA, MeCN). ? ? ? ?Synthesis of the third venetoclax subunit, piperazine amine hydrochloride salt 172, began with commercial cyclohexanone 166. Vilsmeier-Haack formylation of the sterically more accessible enol tautomer of 166 delivered vinyl chloride 167 in quantitative yield. Coupling of this chloride with commercial aryl boronate 168 gave rise to transient enal 169 in 87% assay yield, which was not isolated. Crude 169 was then carried into a reductive amination reaction with commercial N-Boc piperazine (170). Precipitation and recrystallization from acetonitrile ultimately furnished piperazinyl alkene 171 in 74% yield from 167. Finally, subunit 172 was obtained via Boc removal with concentrated HCl in IPA at 65 °C and subsequent filtration, conditions that provided a 95% yield of high purity intermediate 172 (>99.5%).The final approach to venetoclax involved a palladiumcatalyzed coupling of amine 172 with aryl bromide 162, ester hydrolysis, and coupling of the resulting carboxylic acid with sulfonamide 165. In practice, Buchwald-Hartwig amination of 162 with 172 proceeded smoothly and relied upon workup with cysteine to enable cleansing of residual palladium from the reaction mixture. This reaction gave rise to advanced intermediate 173 in 89% yield after crystallization from cyclohexane. Treatment of 173 with t- BuOK/H2O/2-MeTHF at 55 °C provided the corresponding free acid, which was immediately activated with EDC/DMAP/ Et3N to promote coupling with sulfonamide 165 at room temperature. The final drug target could be accessed by crystallization from EtOAc and washing with 1:1 DCM/EtOAc, yielding venetoclax (XVIII) in free base form in 71% over the two final steps. This synthetic route was capable of fashioning the drug target in 52% overall yield based on the longest linear sequence (7 steps).

Definition

ChEBI: A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.

Cytotoxic Activity

Venetoclax displayed cytotoxic activity in various tumour samples/cell lines, including some derived from CLLs, various other NHL subtypes, acute lymphoblastic leukaemias (ALLs), AMLs, chronic myeloid leukaemias (CMLs) and MMs. Notably, the sensitivity of venetoclax correlated with higher BCL-2 expression, with a BCL-2 high status [i.e. BCL-2 gains, BCL-2 amplifications, or the t translocation, which is a notable cause of deregulated BCL-2 expression] and higher BCL-2/MCL-1 ratios being potentially predictive of sensitivity to the drug.

Description

Venetoclax, codeveloped by AbbVie (previously Abbott Laboratories) and Genentech/ Roche, was approved in the US for treatment of patients with chronic lymphocytic leukemia (CLL). To meet qualifications for venetoclax treatment, patients must have received prior therapy and possess the 17p deletion genetic mutation, as determined by USFDA testing. Venetoclax functions as a selective inhibitor of B cell lymphoma subtype 2 (BCL-2), which is often overexpressed on malignant cells and thus leads to impairment of the apoptotic pathway. Along these lines, the orally dosed small molecule drug restores the ability of malignant cells to undergo apoptosis as its mechanism of action.90 Although other BCL-2 inhibitors are known, development of similar agents such as navitoclox have been pursued and halted due to undesired inhibition of BCL-XL, leading to significant thrombocytopenia and demonstrating the need for more selective inhibitors. Venetoclax is also currently being considered for approval in Europe and Canada for similar indications and is in various stages of development for the treatment of non-Hodgkin lymphomas (NHL), acute myeloid leukemia (AML), multiple myeloma (MM), and several other disorders, either as a combination therapy or a stand-alone treatment.

Description

ABT-199, also known as venetoclax, is a small, oral chemical molecule used for the treatment of chronic lymphocytic leukemia (CLL) associated with a specific chromosomal abnormality. As a second line treatment drug of CLL, ABT-199 take effects through acting as a BH3-mimetic and inhibitor of Bcl-2 (the anti-apoptotic B-cell lymphoma-2protein), further inducing apoptosis of CLL cells but not platelets. It also has the potential for the treatment of ER-positive breast cancer.

Mechanism of action

Venetoclax has high affinity for BCL-2, binding to the protein with an affinity more than three orders of magnitude greater than to BCL-XL or BCL-W in vitro. By binding to BCL-2, the drug displaces BCL-2-bound proapoptotic proteins (such as BIM), resulting in the permeabilization of mitochondrial outer membranes, activation of caspases, and restoration of cancer cell apoptosis, with this process requiring the apoptosis regulators BAX or BAK.

References

https://en.wikipedia.org/wiki/Venetoclax Vogler, M, et al. "ABT-199 selectively inhibits BCL2 but not BCL2L1 and efficiently induces apoptosis of chronic lymphocytic leukaemic cells but not platelets." British Journal of Haematology 163.1(2013):139-42. Vaillant, Fran?ois, et al. "Targeting BCL-2 with the BH3 Mimetic ABT-199 in Estrogen Receptor-Positive Breast Cancer." Cancer Cell 24.1(2013):120-9. Lindeman, G. J., et al. "Abstract P2-09-01: Targeting BCL-2 with the BH3 mimetic ABT-199 in ER-positive breast cancer." Cancer Research 73.24 Supplement (2013):P2-09-01-P2-09-01.

1257044-40-8SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name ABT199

1.2 Other means of identification

Product number -
Other names 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

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