856243-80-6
Degrasyn (WP1130)
CAS: 856243-80-6
Molecular Formula: C19H18BrN3O
856243-80-6 - Names and Identifiers
856243-80-6 - Physico-chemical Properties
| Molecular Formula | C19H18BrN3O |
| Molar Mass | 384.27 |
| Density | 1.358 |
| Solubility | Soluble in DMSO (up to 45 mg/ml), or in Ethanol (up to 25 mg/ml). |
| Appearance | solid |
| Color | Yellow |
| Storage Condition | -20° |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. |
| Use | Degrasyn (WP1130) is a selective deubiquitination enzyme (DUB: USP5, UCH-L1, USP9x, USP14, UCH37) inhibitor, also inhibits Bcr/Abl, is also a JAK2 sensor (does not affect 20S proteasome) and transcription activator (STAT). |
| In vitro study | In addition to inducing rapid down-regulation of Bcr/Abl without affecting Bcr or c-Abl, WP1130 also regulates the stability of Jak2 and c-Myc without affecting other kinases (HER1, HER2, c-Kit, FAK, ERK1, ERK2, Akt, Btk, Src and Src-related kinases) or transcription factors (wild-type p53, STAT1, STAT3 STAT5, c-Jun, NF-κB, and Max). Unlike adaphostin and Trisenox, WP1130 induces down-regulation of Bcr/Abl within 60 minutes. WP1130 is more effective in inducing apoptosis of myeloid and lymphoid tumor cells with IC50 of ~0.5-2.5 μM compared with normal CD34 hematopoietic precursors, dermal fibroblasts, or endothelial cells with IC50 ~ 5-10 μM. WP1130 (5 μM) specifically and rapidly down-regulates both wild-type and T315I mutant Bcr/Abl protein without affecting bcr/abl gene expression or engaging the proteasomal degradation pathway in chronic myelogenous leukemia (CML) cells, accompanied by induction of apoptosis. WP1130 is more effective in reducing leukemic cell colony formation compared with normal progenitor cells and effective against primary leukemic cells harboring the T315I mutation. WP1130 induces rapid proteasomal-dependent degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines, correlated with tumor growth inhibition. Unlike AG490, WP1130 acts as a partly selective deubiquitinase (DUB) inhibitor to induce a rapid and marked accumulation of polyubiquitinated (K48/K63-linked) proteins into juxtanuclear aggresomes without affecting proteasome activity. WP1130 (5 μm) directly inhibited DUB activity of USP9x, USP5, USP14, UCH-L1, and UCH37, but not UCH-L3, resultant, In addition to inducing rapid Bcr/Abl downregulation without affecting Bcr or MCL-1, WP1130 also modulates the stability of Jak2 and c-Abl, without affecting other kinases (HER1,HER2,c-Kit,FAK,ERK1,ERK2,Akt,Btk,Src Kinases associated with Src) or transcription factors (wild-type p53,STAT1,STAT3,STAT5,c-Jun,NF-κB, and Max). Unlike adaphostin and Tris Enox, WP1130 induced Bcr/Abl downregulation within 60 minutes. With normal CD34 in MM-1 multiple myeloma and other tumor cell lines, WP1130 induced rapid proteasome-dependent c-Myc protein degradation, associated with inhibition of tumor growth. Unlike AG490,WP1130, as a partially selective deubiquitinating enzyme (DUB) inhibitor, induces rapid and significant polyubiquitination (K48/K63 ligation) the protein aggregates into nuclear-like aggregates without affecting proteasome activity. WP1130 (5 μm) directly inhibits the DUB activity of USP9x,USP5,USP14, UCH-L3, and UCH37 in addition to UCH-L1, leading to down-regulation of anti-apoptotic and pro-apoptotic proteins, such as MCL-1 and an increase in p53. |
| In vivo study | Administration of WP1130 inhibitors the growth of K562 tumors as well as both wild type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells Trans. Consistent with the down-regulation of c-Myc, WP1130 displays potential activity against A375 melanoma tumors established in nude mice. WP1130 administration inhibited the growth of K562 tumors transplanted into nude mice, as well as wild-type Bcr/Abl and T315I mutant Bcr/Abl expressing BaF/3 cells. In line with the down-regulation of c-Myc, WP1130 showed potent inhibition of established A375 melanoma in nude mice. |
856243-80-6 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.602 ml | 13.012 ml | 26.023 ml |
| 5 mM | 0.52 ml | 2.602 ml | 5.205 ml |
| 10 mM | 0.26 ml | 1.301 ml | 2.602 ml |
| 5 mM | 0.052 ml | 0.26 ml | 0.52 ml |
Last Update：2024-01-02 23:10:35
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Product Name: Degrasyn (WP1130) Visit Supplier Webpage Request for quotation
CAS: 856243-80-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 856243-80-6
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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