• Search chemicals, activators, Inhibitors, APIs, intermediates and raw materials.

877877-35-5 (TW-37)

1

Identification

TW-37 TW-37
Name TW-37
Formula C33H35NO6S
MW 573.7
CAS No. 877877-35-5
EINECS
Smiles O=C(C1=CC(CC2=CC=CC=C2C(C)C)=C(C(O)=C1O)O)NC3=CC=C(C=C3)S(=O)(C4=CC=CC=C4C(C)(C)C)=O
Synonyms TW 37;TW37; N-(4-((2-(tert-butyl)phenyl)sulfonyl)phenyl)-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide
InChI InChI=1S/C33H35NO6S/c1-20(2)25-11-7-6-10-21(25)18-22-19-26(30(36)31(37)29(22)35)32(38)34-23-14-16-24(17-15-23)41(39,40)28-13-9-8-12-27(28)33(3,4)5/h6-17,19-20,35-37H,18H2,1-5H3,(H,34,38)
2

Introduction

TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. IC50 Value: 0.29 μM (Ki for Bcl-2) Target: Bcl-2 Family in vitro: TW-37 shows significant anti-proliferative and pro-apoptotic effect in a de novo chemo-resistant WSU-DLCL2 lymphoma cell line and primary cells obtained from a lymphoma patient without effects on normal peripheral blood lymphocytes.

Background Information

TW-37 is a potent small-molecule inhibitor of BCL-2 (Ki = 290 nmol/L), which attenuates BCL-2 activation and inhibits multiple BCL-2 family members including BCL-XL (Ki = 1,110 nmol/L) and MCL-1 (Ki = 260 nmol/L). It binds to the BCL-2 homology domain 3 (BH3) groove of BCL-2 preventing the heterodimerization of proapoptotic proteins (such as Bid, Bim, and Bad) with BCL-2 and subsequently allowing them to induce apoptosis. Recent studies indicate TW-37 is able to inhibit the growth of a broad range of cancer cells (such as breast, prostate, lymphoma, and pancreatic cancer), since it induces S-phase cell cycle arrest with regulation of several important cell cycle related genes, including p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1 and cyclin E.

Reference

Zhiwei Wang, Asfar Sohail Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H. Sarkar, and Ramzi M. Mohammad. TW-37, a small-molecule inhibitor of BCL-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer Res 2009;69:2757-2765

Naoki Ashimori, Benjamin D. Zeitlin, Zhaocheng Zhang, Kristy Warner, IIan M. Turkienicz, Aaron C. Spalding, Theodoros N. Teknos, Shaomeng Wang, and Jacques E. Nor. TW-37, a small-molecule inhibitor of BCL-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol Cancer Ther 2009;8:893-903

......by Apexbio Technology LLC
TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1. ......by BOC Sciences
TW-37 is a potent Bcl-2 inhibitor with Ki values of 260, 290 and 1110 nM for Mcl-1, Bcl-2 and Bcl-xL, respectively. ......by MedChemexpress Co., Ltd.
TW-37 is a small-molecule inhibitor of Bcl-2 family proteins, inhibited cell growth and induced apoptosis in pancreatic cancer. TW-37 induces cell growth inhibition and S-phase cell cycle arrest, with regulation of several important cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1, and cyclin E. The cell growth inhibition was accompanied by increased apoptosis with concomitant attenuation of Notch-1, Jagged-1, and its downstream genes such as Hes-1 in vitro and in vivo. Shelf life: >2 years if stored properly Drug formulation: ......by MedKoo Biosciences, Inc.
TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM in cell-free assays, respectively. ......by Selleck Chemicals LLC
TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. ......by Target Molecule Corp.
Bcl-2 inhibitor (Ki values are 0.29 μM and 1.11 μM for Bcl-2 and Bcl-XL respectively). Inhibits the angiogenic potential of endothelial cells in vitro. Induces S-phase arrest and apoptosis in pancreatic cancer cell lines; also inhibits the activation of Notch-1 and Jagged-1 in vitro and in vivo. ......by Tocris Bioscience Inc.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines BxPC-3 and Colo-357 cells
Conditions 750 nM, 72 hours for cell growth inhibition 500 nM, 48 hours for apoptosis induction (measured by Annexin V)
Method The cell viability was assessed by the clonogenic assay. TW-37 resulted in a significant inhibition of colony formation of BxPC-3 and Colo-357 cells when compared with control. Besides that, TW-37 induced apoptosis in a dose- and time-dependent manner. In the Annexin V assay, the percentage of apoptotic cells increased from 5% to 6% in the control to 12% to 14% in both BxPC-3 and Colo-357 cell lines.
Source Apexbio Technology LLC
Cell lines HDMECs
Conditions 0 - 100 μM; 96 hours
Method The sulforhodamine B (SRB) cytotoxicity assay is used as described. Briefly, optimal cell density for cytotoxicity assay is determined by growth curve analysis. HDMECs are seeded in a 96-well plate and allowed to adhere overnight. Drug or control is diluted in EGM2-MV and layered onto cells, which are allowed to incubate for times as indicated in the figures. Alternatively, HDMECs are coincubated with TW37 and 0 to 100 ng/mL recombinant human VEGF (rhVEGF)165 or 0 to 100 ng/mL recombinant human CXCL8. Cells are fixed on the plates by addition of cold trichloroacetic acid (10% final concentration) and incubation for 1 hour at 4 °C. Cellular protein is stained by addition of 0.4% SRB in 1% acetic acid and incubation at room temperature for 30 minutes. Unbound SRB is removed by washing with 1% acetic acid and the plates are air dried. Bound SRB is resolubilized in 10 mM unbuffered Tris-base and absorbance is determined on a microplate reader at 560 nm. Test results are normalized against initial plating density and drug-free controls. Data are obtained from triplicate wells per condition and are representative of at least three independent experiments
Source Selleck Chemicals LLC

Animal Experiment

Animal Models Female ICR-SCID mice bearing Colo-357 xenografts
Dosage Form Intravenous injection, 20 mg/kg/d
Applications TW-37 treatment significantly inhibited pancreatic tumor growth in vivo. Western blot analysis showed that the expression level of Notch-1 was significantly lower in tumors from the TW-37–treated mice than those from vehicle-treated control mice. In addition, the expression of Jagged-1 and Notch-1 downstream target gene, Hes-1, was also down-regulated in TW-37–treated tumors.
Source Apexbio Technology LLC
Animal Models Athymic NCr-nu/nu mice bearing SK-Mel-147 melanoma xenografts
Dosage ~40 mg/kg
Formulation TW-37 is resuspended in 1:1 Tween 80/ethanol (diluted 10-fold in 0.9% saline before use).
Administration Administered via i.v. or i.p.
Source Selleck Chemicals LLC
4

Physical and Chemical Properties

Appearance:White to off-white Solid EBNumber:EB000029011

Storage condition

Store at -20°C by Apexbio Technology LLC
Store at -20°C by Tocris Bioscience Inc.

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
DMSO ≥112mg/mL Water <1.2mg/mL Ethanol ≥3.7mg/mL by MedChemexpress Co., Ltd.
(25°C) * In vitro DMSO 115 mg/mL (200.45 mM); Ethanol4 mg/mL (6.97 mM); Water<1 mg/mL (<1 mM); In vivo 30% Propylene glycol, 5% Tween 80, 65% D5W30 mg/mL by Selleck Chemicals LLC
Soluble to 100 mM in DMSO by Tocris Bioscience Inc.
5

Mechanism and Indication

Signaling Pathways Apoptosis
Target Bcl-2 Family
Research Area Cancer
Indications
6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
TW-37 - Not Found
TW-37 - No Development Reported
7

Safety Data of TW-37

8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
Apexbio Technology LLC USA
BOC Sciences
Biochem Tek(Shanghai) Co., ltd. China
Biochempartner Co., Ltd China
CHEMSCENE, LLC 10mg/USD160();50mg/USD650() USA
MedChemexpress Co., Ltd. 10mg/USD160();50mg/USD650() USA
MedKoo Biosciences, Inc. USA
Selleck Chemicals LLC 10mM/1mLIn DMSO/USD146(In stock);10mg/USD160(In stock);50mg/USD680(In stock);200mg/USD1480(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 10mg/USD160();50mg/USD650() China
Target Molecule Corp. 2mg/USD51();5mg/USD88();10mg/USD148();25mg/USD268();50mg/USD408() USA
Tocris Bioscience Inc. USA
10

Related Products

Other Forms of 877877-35-5

Name CAS No Formula MW

Recommended Compounds in Bcl-2 Family

Name CAS No Formula MW
MIM1 509102-00-5 C17H21N3O3S 347.43
713492-66-1
Gossypol (acetic acid) 12542-36-8 C32H34O10 578.6064
Marinopyrrole A 1227962-62-0 C22H12Cl4N2O4 510.15
WEHI-539 1431866-33-9 C31H29N5O3S2 583.72
Gambogic Acid 2752-65-0 C38H44O8 628.75
ABT-199 1257044-40-8 C45H50ClN7O7S 868.44
(±)-Apogossypol 475-56-9 C28H30O6 462.5342
Gossypol 303-45-7 C30H30O8 518.55
AT-101 90141-22-3 C30H30O8 518.55
BAM7 331244-89-4 C21H19N5O2S 405.47
SZ4TA2 406231-90-1 C28H32N4O5S2 568.71
HA14-1 65673-63-4 C17H17BrN2O5 409.23
Obatoclax 803712-79-0 C21H23N3O4S 413.49
ABT-737 852808-04-9 C42H45ClN6O5S2 813.43
Navitoclax 923564-51-6 C47H55ClF3N5O6S3 974.61
Bax inhibitor peptide V5 579492-81-2 C27H50N6O6S 586.79
A-1331852 1430844-80-6 C38H38N6O3S 658.81
A-1155463 1235034-55-5 C35H32FN5O4S2 669.79
Bz 423 216691-95-1 C27H21ClN2O2 440.92

Recommended Compounds in Same Indication

Name CAS No Formula MW
11

Route of Synthesis

12

References

[1]. Ashimori et al (2009) TW-37, a small molecule inhibitor of Bcl-2, mediates S phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol.Cancer.Ther. 8 893.

[2]. Wang et al (2009) TW-37, a small molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer Res. 69 2757.

[3]. Zeitlin BD, Spalding AC, Campos MS, Ashimori N, Dong Z, Wang S, Lawrence TS, N?r JE.Metronomic small molecule inhibitor of Bcl-2 (TW-37) is antiangiogenic and potentiates the antitumor effect of ionizing radiation.Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):879-87. Epub 2010 Aug 1.

[4]. Al-Katib AM, Sun Y, Goustin AS, Azmi AS, Chen B, Aboukameel A, Mohammad RM.SMI of Bcl-2 TW-37 is active across a spectrum of B-cell tumors irrespective of their proliferative and differentiation status.J Hematol Oncol. 2009 Feb 16;2:8.

[5]. Wang Z, Song W, Aboukameel A, Mohammad M, Wang G, Banerjee S, Kong D, Wang S, Sarkar FH, Mohammad RM.TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer.Int J Cancer. 2008 Aug 15;123(4):958-66.

Protocol Reference

[1] Wang Z, Azmi A S, Ahmad A, et al. TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer research, 2009, 69(7): 2757-2765.

......by Apexbio Technology LLC
Wang et al (2006) Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J.Med.Chem. 49 6139. PMID: 17034116.

Zeitlin et al (2006) Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2. Cancer Res. 66 8698. PMID: 16951185.

Ashimori et al (2009) TW-37, a small molecule inhibitor of Bcl-2, mediates S phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol.Cancer.Ther. 8 893. PMID: 19372562.

......by Tocris Bioscience Inc.

13

More Information

TW-37

Tags: buy 877877-35-5 IC50 | 877877-35-5 price | 877877-35-5 cost | 877877-35-5 solubility | 877877-35-5 purchase | 877877-35-5 manufacturer | 877877-35-5 research buy | 877877-35-5 order | 877877-35-5 MSDS | 877877-35-5 chemical structure | 877877-35-5 Storage condition | 877877-35-5 molecular weight | 877877-35-5 mw | 877877-35-5 datasheet | 877877-35-5 supplier | 877877-35-5 cell line | 877877-35-5 NMR | 877877-35-5 MS | 877877-35-5 IR | 877877-35-5 solubility | 877877-35-5 Safe information | 877877-35-5 Qc and Spectral Information | 877877-35-5 Clinical Information | 877877-35-5 Clinical Trial | 877877-35-5 Route of Synthesis | 877877-35-5 storage condition | 877877-35-5 diseases and conditions | 877877-35-5 flash point | 877877-35-5 boiling point | 877877-35-5 melting point | 877877-35-5 storage condition | 877877-35-5 brand