description ABT-737 and ABT-263 Biological activity In vitro In vivo Feature
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ABT 737

description ABT-737 and ABT-263 Biological activity In vitro In vivo Feature
Product Name
ABT 737
CAS No.
852808-04-9
Chemical Name
ABT 737
Synonyms
ABT 737;CS-1870;Dibenz[a;CCRIS 208;h]anthracene;ABT-737, >=98%;ABT737/ABT-737;ABT 737 USP/EP/BP;ABT-737;ABT737;ABT 737;Bcl-2 Inhibitor VI, ABT-737 - CAS 852808-04-9 - Calbiochem
CBNumber
CB51872885
Molecular Formula
C42H45ClN6O5S2
Formula Weight
813.43
MOL File
852808-04-9.mol
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ABT 737 Property

Melting point:
152-154°C
Density 
1.38±0.1 g/cm3(Predicted)
storage temp. 
Keep in dark place,Sealed in dry,Store in freezer, under -20°C
solubility 
DMSO (Slightly), Methanol (Slightly, Heated, Sonicated)
form 
Yellow solid
pka
4.65±0.10(Predicted)
color 
Light Yellow to Yellow
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Safety

HS Code 
29309090
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
197333
Product name
Bcl-2 Inhibitor VI, ABT-737 - CAS 852808-04-9 - Calbiochem<br />The Bcl-2 Inhibitor VI, ABT-737, also referenced under CAS 852808-04-9, controls the biological activity of Bcl-2. This small molecule/inhibitor is primarily used for Activators/Inducers applications.
Packaging
10mg
Price
$280
Updated
2024/03/01
Cayman Chemical
Product number
11501
Product name
ABT-737
Purity
≥98%
Packaging
1mg
Price
$28
Updated
2024/03/01
Cayman Chemical
Product number
11501
Product name
ABT-737
Purity
≥98%
Packaging
5mg
Price
$76
Updated
2024/03/01
Cayman Chemical
Product number
11501
Product name
ABT-737
Purity
≥98%
Packaging
10mg
Price
$125
Updated
2024/03/01
Cayman Chemical
Product number
11501
Product name
ABT-737
Purity
≥98%
Packaging
25mg
Price
$241
Updated
2024/03/01
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ABT 737 Chemical Properties,Usage,Production

description

ABT-737 is a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with potential pro-apoptotic and antineoplastic activities,  with an affinity two to three orders of magnitude more potent than previously reported compounds but no affinity towards less homologous proteins, such as BCL-B, MCL-1, and A1. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumors, and produces cures in a high percentage of the mice. ABT-737 binds to Bcl-2, Bcl-xL and Bcl-w with very high affinities (Ki <1 nM) and also shows a very high specificity over Mcl-1 and A1.
ABT-737 induces apoptosis in MM cells, including those resistant to conventional therapy. Importantly, ABT-737 decreases the viability of bortezomib-, dexamethasone-(Dex) and thalidomide-refractory patient MM cells. Additionally, ABT-737 abrogates MM cell growth triggered by interleukin-6 or insulin-like growth factor-1. Mechanistic studies show that ABT-737-induced apoptosis is associated with activation of caspase-8, caspase-9 and caspase-3, followed by poly(ADP-ribose) polymerase cleavage.
ABT-737 has shown single-agent activity against lymphoma and small-cell lung cancer as well as substantial antimyeloma activity both in vitro and in vivo. In recent studies, acute myeloid leukemia blast, origenitor, and stem cells are effectively killed by ABT-737 with normal hematopoietic cells intact. The disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway could also be induced by ABT-737.

ABT-737 and ABT-263

Both are small molecules designed to bind to the key p2 and p4 hotspots of Bcl-2 and Bcl-XL. ABT-737 as single agent exhibits effective antitumor activity in vitro against lymphoma and small-cell carcinoma cells, and also in mouse xenograft models with high expression of Bcl-2 or Bcl-XL. However, ABT-737 has low solubility and oral bioavail- ability in contrast to ABT-263, which is a second-generation ABT-737 with the same mechanism of action. Phase-I and phase-II c linical trials showed that both ABT-263 and ABT-737 were effective in CLL and small-cell lung cancer (SCLC) as a single agent. While they are useful as a single agent, ABT-737 and ABT-263 have significant synergistic effects in inducing apoptosis when combined with other antitumor drugs. ABT-263 has been shown to enhance the therapeutic effect of radiation therapy and chemotherapy for SCLC, follicular lymphoma, CLL, so on, while ABT-737 sensitized cancer cells for flavopiridol, arsenic trioxide, or fenretinide. Additional studies showed that ABT- 263 sensitized conventional agents, such as fludarabine, cyclophosphamide, and rituximab, in treating many solid tumors. However, both ABT-737 and ABT-263 can reduce platelet for targeting Bcl-Xl, which is required in maintaining the lifespan of circulating platelet, requesting the development of selective Bcl-2 inhibitors.
Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy, Volume 4 1st Edition

Biological activity

ABT-737 is a kind of BH3 mimic inhibitor, acting on Bcl-xL, Bcl-2 and Bcl-w, with the EC50 being 78.7 nM, 30.3 nM and 197.8 nM in cell-free assays; However, it has no inhibitory effect on Mcl-1, Bcl-B and Bfl-1.
ABT737 up-regulates the expression of apoptosis-related gene Bim through JNK/c-Jun signaling pathway, and induce the apoptosis of Hela cells.
Use MTT assay to measure the inhibitory effect of ABT-737 on the growth of human cervical cancer Hela cells; apoptosis rate was detected by flow cytometry; the expression of JNK, phospho-JNK, c-Jun and phospho-c-Jun were detected by Western blot; the mRNA expression of Bim protein was detected by RT-PCR. The activity of JNK and c-Jun was inhibited by transiently transfect of the JNK-specific inhibitor SP600125 and siRNA.
ABT-737 can inhibit the growth of HeLa cells and induce HeLa cells to encounter apoptosis. ABT737 can activate the JNK kinase activity as well as its downstream target molecule c-Jun, further up-regulating the mRNA expression and protein expression of apoptosis-related gene Bim. ABT737-induced up-regulation of Bim and apoptosis were also blocked through inhibiting the activity or the expression of JNK or c-Jun by JNK-specific inhibitor SP600125 and siRNA targeting JNK and c-Jun.
This information is compiled and edited by Xiao Nan from Chemicalbook.

In vitro

ABT-737 shows low activity to Bcl-B and no effects to Mcl-1 and BFL-1. ABT-737 is sensitive to HL60, KG1 and NB4 cells with IC50 of 50 nM, 80 nM and 80 nM, respectively. ABT-737 induces apoptosis in HL60 cells, which due to decreased Bcl-2/Bax heterodimerization and has no effect on cell cycle distribution. ABT-737 also induces cytochrome c release from purified mitochondria and promotes conformational changes in Bax that are associated with apoptosis.Resistant cells (Hela and MCF-7) can be sensitized to ABT-737 by approaches that down-regulate, destabilize, or inactivate Mcl-1. ABT-737 also causes Bax/BAK-dependent cytochrome c release only when Mcl-1 has been neutralized.ABT-737 displaces Bim from Bcl2's BH3-binding pocket, allowing Bim to activate Bax, induce mitochondrial permeabilization, and rapidly commit the primary chronic lymphocytic leukemia (CLL) cells to death.  Knockdown of Mcl-1 with siRNA sensitizes two resistant SCLC cell lines H196 and DMS114 to ABT-737 by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitizes H196 cells to ABT-737. ABT-737 inhibits proliferation and induces apoptosis in many SCLC cell lines including NCI-H889, NCI-H1963, NCI-H1417, NCI-H146 and etc. Bcl-2 and Noxa may contribute mechanistically to the cellular response to ABT-737 in NCI-H146 cells. A recent study shows that ABT-737 significantly induces apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells. 

In vivo

In aggressive leukemia model, ABT-737 suppresses the leukemia burden by 53% at the 30 mg/kg, with significantly extended survival of mice. ABT-737 does not induce significantly abnormalities in blood cell counts or serum chemistries.  ABT-737 prolongs the survival of recipient mice transplanted with Bcl-2-transduced tumors. ABT-737 shows great antitumor activity in an ATLL mouse model at a dose of 100 mg/kg. 

Feature

ABT-737 is the first-generation small molecule inhibitors of the anti-apoptotic BCL-2 family protein.

Chemical Properties

Yellow Solid

Uses

ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM, respectively.

Uses

A selective inhibitor of BCL-2, in small cell lung cancer. ABT-737 induced dramatic regressions in tumors derived from some SCLC cell lines.

Definition

ChEBI: ABT-737 is a biphenyl that is 4-chloro-1,1'-biphenyl substituted by a (4-{4-[(4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzene-1-sulfonyl)carbamoyl]phenyl}piperazin-1-yl)methyl group at position 2'. It is a BH3-mimetic drug which targets the anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, and induces apoptosis in cancer cells. It has a role as an anti-allergic agent, an anti-inflammatory agent, an antineoplastic agent, an apoptosis inducer and a B-cell lymphoma 2 inhibitor. It is a member of biphenyls, a member of monochlorobenzenes, a C-nitro compound, an aromatic amine, a N-arylpiperazine, a N-sulfonylcarboxamide, an aryl sulfide, a secondary amino compound and a tertiary amino compound.

Biological Functions

ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in cell-free assays, respectively; no inhibition observed against Mcl-1, Bcl-B or Bfl-1. ABT-737 induces mitochondrial pathway apoptosis and mitophagy. Phase 2.

Biological Activity

abt-737 is a novel and potent inhibitor of b-cell lymphoma 2 (bcl-2) family proteins, which are critical for cell survival and overexpressed in many tumor cells, with high affinity towards bcl-xl, bcl-2, and bcl-w but no affinity towards less homologous proteins, such as bcl-b, mcl-1, and a1. abt-737 has shown single-agent activity against lymphoma and small-cell lung cancer as well as substantial antimyeloma activity both in vitro and in vivo. in recent studies, acute myeloid leukemia blast, origenitor, and stem cells are effectively killed by abt-737 with normal hematopoietic cells intact. the disruption of the bcl-2/bax complex and bak-dependent but bim-independent activation of the intrinsic apoptotic pathway could also be induced by abt-737.marina konopleva, rooha contractor, twee tsao, ismael samudio, peter p. ruvolo, shinichi kitada, xingming deng, dayong zhai, yue-xi shi, thomas sneed, monique verhaegen, maria soengas, vivian r. ruvolo, teresa mcqueen, wendy d. schober, julie c. watt, tilahun jiffar, xiaoyang ling, frank c. marini, david harris, martin dietrich, zeev estrov, james mccubrey, w. stratford may, john c. reed, and michael andreeff. mechanisms of apoptosis sensitivity and resistance to the bh3 mimetic abt-737 in acute myeloid leukemia. cancer cell 2006: 10; 375-388suzanne trudel, a. keith stewart, zhihua li, yanjun shu, sheng-ben liang, young trieu, donna reece, josh paterson, dingyan wang, and xiao-yan wen. the bcl-2 family protein inhibitor,abt-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalan. clin cancer res 2007; 13 (2) 621-629

storage

Store at -20°C

ABT 737 Preparation Products And Raw materials

Raw materials

Preparation Products

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ABT 737 Suppliers

Zhengzhou HSH Science & Technology Co., Ltd.
Tel
0371-55932928 18937192232
Email
1282296214@qq.com
Country
China
ProdList
496
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55
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2923
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55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
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76
Chembest Research Laboratories Limited
Tel
021-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6013
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61
JinYan Chemicals(ShangHai) Co.,Ltd.
Tel
13817811078
Fax
86-021-50426522,50426273
Email
sales@jingyan-chemical.com
Country
China
ProdList
9984
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60
Nanjing Chemlin Chemical Co., Ltd
Tel
025-83697070 13913916777;
Fax
+86-25-83453306
Email
info@chemlin.com.cn
Country
China
ProdList
17839
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64
Chemsky(shanghai)International Co.,Ltd.
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
32344
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50
Jinan Trio PharmaTech Co., Ltd.
Tel
+86 (531) 88811783
Fax
+86 (531) 55696010 QQ 1762738062
Email
sales@trio-pharmatech.com (International market)
Country
China
ProdList
1856
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62
ChemCell Biomedicine Co.,Ltd.
Tel
020-13556033878 2965585218 13556033878
Fax
0086-0757-85406358
Email
chemcell@hotmail.com
Country
China
ProdList
369
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52
Xi’an chemsoar Medical Technology Co., ltd
Tel
029-86538357
Fax
029-87871708
Country
China
ProdList
234
Advantage
57
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View Lastest Price from ABT 737 manufacturers

Career Henan Chemical Co
Product
ABT 737 852808-04-9
Price
US $2.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
customsie
Release date
2018-08-20

852808-04-9, ABT 737Related Search:


  • 4-[4-[(4'-Chloro[1,1'-biphenyl]-2-yl)methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl]amino]-3-nitrophenyl]sulfonyl]benzamide
  • ABT 737
  • 4-{4-[(4'-Chlorobiphenyl-2-yl)Methyl]piperazin-1-yl}-N-[(4-{[(2R)-4-(diMethylaMino)-1-(phenylsulfanyl)butan-2-yl]aMino}-3-nitrophenyl)sulfonyl]benzaMide
  • (R)-4-(4-((4'-chlorobiphenyl-2-yl)Methyl)piperazin-1-yl)-N-(4-(4-(diMethylaMino)-1-(phenylthio)butan-2-ylaMino)-3-nitrophenylsulfonyl)benzaMide
  • BenzaMide, 4-[4-[(4'-chloro[1,1'-biphenyl]-2-yl)Methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(diMethylaMino)-1-[(phenylthio)Methyl]propyl]aMino]-3-nitrophenyl]sulfonyl]-
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  • ABT737/ABT-737
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  • ABT-737 4-[4-[(4'-Chloro[1,1'-biphenyl]-2-yl)methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl]amino]-3-nitrophenyl]sulfonyl]benzamide
  • ABT-737, >=98%
  • BenzaMide, 4-[4-[(4'-chloro[1,1'-biphenyl]-2-yl)Methyl]-1-piperazinyl]-N-[[4-[[(1R)-3-(diMethylaMino)-1-[(phenylthio)Methyl]propyl]aMin
  • ABT-737;ABT737;ABT 737
  • CS-1870
  • Bcl-2 Inhibitor VI, ABT-737 - CAS 852808-04-9 - Calbiochem
  • ABT 737 USP/EP/BP
  • (R)-4-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenyl)sulfonyl)benzamide
  • 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide
  • CCRIS 208
  • Dibenz[a
  • h]anthracene
  • N-{4-[4-(4'-chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzoyl}-4-((R)-3-dimethylamino-1-phenylsulfanylmethyl-propylamino)-3-nitro-benzenesulfonamide
  • 852808-04-9
  • C42H45ClN6O5S2
  • Inhibitor
  • Chiral Reagents
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
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