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|Synonyms:||ABT-199;ABT199,GDC0199;GDC 0199;GDC0199;GDC-0199;4-[4-[[2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-benzamide;Benzamide, 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-;4-[4-[[2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-benzamide ABT-199 (GDC-0199)|
|ABT-199 Chemical Properties|
|ABT-199 Usage And Synthesis|
|A new type of anti-cancer drugs||
ABT-199 is a novel anti-cancer drug, and a Bcl-2 inhibitor, which is researched and developed by by the US pharmaceutical company Abbvie (AbbVie).It is effective against cancer, and makes a small side effects compared to the current drugs, The study is carried out by US and Australian researchers, and their research results were published in the international journal Nature Medicine.
It is different from common cancer drugs: this drug named ABT-199 attacks one kind of important proteins referred as BCL-2 to play an important role in the treatment of cancer. BCL-2 is the first discovered member of cell death regulating BCL-2 protein family . It is associated with many types of cancer, as well as some psychiatric disorders and autoimmune diseases. In cancer, people think it acts as a repressor that can help cancer cells to resist cancer treatments.
In the treatment of cancer, cancer cells can make use of pro-survival BCL-2 protein to inhibit the therapeutic effect of conventional chemotherapy, which often gives clinicians headache. It is also because the cancer cells can be make use of pro-survival BCL-2 protein to inhibit the therapeutic effect of conventional chemotherapy, that makes clinical doctors have to increase the dose again and again, which leads to the side effects of chemotherapy, such as nausea, hair loss and so on.
ABT-199 emerging as a drug to eliminate and reduce the occurrence of BCL-2, makes many clinicians see the dawn of cancer treatment. ABT-199 as a novel anti-cancer drug, can inhibit the growth of BCL-2, without affecting BCL-XL--a protein necessary for platelet formation . Overcoming this problem, is completely worth cheering in the history of the treatment of cancer.
[Clinical Trial Evaluation] clinical trial phase I (NCT01328626) enrolls 84 patients with relapsed type/refractory CLL/SLL and 44 patients with relapsing/refractory non-Hodgkin's lymphoma . ABT-199 treatment of CLL/SLL response rate is 79% (complete response rate was 22%), median durative response time is 20.5 months; ABT-199 treatment of non-Hodgkin's lymphoma response rate is 48% (complete The response rate was 7.5%). The efficacy of ABT-199 is well matched with obinutuzumab, idelalisib, ibrutinib. ABT-199 is expected to be the first Bcl-2 inhibitor on the market.
The above information is edited by the chemicalbook of Tian Ye.
|Biological Activity||ABT-199 (GDC-0199) is a selective inhibitor of Bcl-2, Ki is <0.01 nM in a cell-free assay , selectivity in Bcl-2 is over 4800 times higher than that in Bcl-xL and Bcl-w ,it has no inhibitory activity in Mcl-1 .|
|In vitro studies||ABT-199 has a low sensitivity to Bcl-xL, Mcl-1 and Bcl-w , Ki is 48 nM,> 444 nM and 245 nM. ABT-199 effectively inhibits FL5.12-Bcl-2cells, RS4; 11 cells, EC50 is 4 nM and 8 nM, it has low activity on FL5.12-Bcl-xLcells , EC50 is 261 nM. ABT-199 induces RS4; 11 cells into apoptosis rapidly and releases cytochrome c , activates caspase , externalizes phosphatidylserine and accumulates sub-G0/G1 DNA . Quantitative immunoblotting shows, ABT-199 sensitivity to cell lines including NHL, DLBCL, MCL, AML and ALL , is strongly related to Bcl-2 expression . ABT-199 also induces apoptosis of CLL, the mean EC50 is 3.0 nM.|
|In vivo studies||ABT-199 (100 mg/kg) treats RS4; 11 xenografts, maximum growth inhibition of the tumors is 95%, tumor growth delays 152%. ABT-199 alone or in combination with SDX-105 or other agents treating DoHH2 and Granta-519 xenografts, also inhibits tumor growth.|
|Characteristics||ABT-263 (Navitoclax) restructuring.|
|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.|