Synonym
HBX 41108; HBX-41108; HBX41108; HBX 41,108; HBX-41,108; HBX41,108.
IUPAC/Chemical Name
7-Chloro-9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile
InChi Key
BIGPXXAUSQLTQR-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H3ClN4O/c14-6-1-2-7-8(3-6)13(19)12-11(7)17-9(4-15)10(5-16)18-12/h1-3H
SMILES Code
N#CC1=C(C#N)N=C2C(C(C3=C2C=CC(Cl)=C3)=O)=N1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
HBX 41108 is an inhibitor of ubiquitin-specific protease (USP) 7 activity (IC50 = 424 nM). Also inhibits USP7-mediated p53 deubiquitination (IC50 = 0.8 μM).
In vitro activity:
Moreover, the proportion of cells in the G0/G1 phase was significantly increased by AGEs, which was decreased by USP7 knockdown or HBX 41108, whereas that of cells in the S phase was significantly decreased by AGEs, which was increased by USP7 knockdown or HBX 41108 (Figure 2D,E). In addition, AGEs markedly increased the level of cell senescence, whereas the inhibition of USP7 by shUSP7 or HBX 41108 could reverse this effect (Figure 2F). p53 and p21 are markers of cell senescence. Western blot analysis revealed that the expressions of p53 and p21 were elevated by AGEs and decreased by shUSP7 and HBX 41108 (Figure 2G,H). These results indicated that inhibition of USP7 expression and its deubiquitinating activity could reduce cell cycle arrest and cell senescence in HUVECs.
Reference: Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):311-320. https://pubmed.ncbi.nlm.nih.gov/35538032/
In vivo activity:
Treatment of diabetic rats with HBX 41108 decreased blood glucose levels on 14 post-injury (Figure 5A). STZ (streptozotocin) significantly reduced the wound healing rate, whereas the application of HBX 41108 could rescue the STZ-mediated effects (Figure 5B,C). HE staining of tissue sections showed that epithelial tissue was newly formed in wounds treated with HBX 41108 on day 7 post-injury (Figure 5D). Meanwhile, on day 7 and day 14, the expressions of USP7, p53, and p21 were found to be increased by STZ and decreased by the application of HBX 41108 (Figure 5E). These results showed that HBX 41108 could facilitate wound healing in diabetic rats through inhibiting USP7 deubiquitinating activity.
Reference: Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):311-320. https://pubmed.ncbi.nlm.nih.gov/35538032/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
25.0 |
93.76 |
| DMSO |
29.8 |
111.87 |
| DMSO:PBS (pH 7.2) (1:40) |
0.2 |
0.75 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
266.64
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Li X, Wang T, Tao Y, Wang X, Li L, Liu J. Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53. Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):311-320. doi: 10.3724/abbs.2022003. PMID: 35538032.
In vitro protocol:
1. Li X, Wang T, Tao Y, Wang X, Li L, Liu J. Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53. Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):311-320. doi: 10.3724/abbs.2022003. PMID: 35538032.
In vivo protocol:
1. Li X, Wang T, Tao Y, Wang X, Li L, Liu J. Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53. Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):311-320. doi: 10.3724/abbs.2022003. PMID: 35538032.
1: Nicholson B, Suresh Kumar KG. The multifaceted roles of USP7: new therapeutic
opportunities. Cell Biochem Biophys. 2011 Jun;60(1-2):61-8. doi:
10.1007/s12013-011-9185-5. Review. PubMed PMID: 21468693.
2: Colland F, Formstecher E, Jacq X, Reverdy C, Planquette C, Conrath S, Trouplin
V, Bianchi J, Aushev VN, Camonis J, Calabrese A, Borg-Capra C, Sippl W, Collura
V, Boissy G, Rain JC, Guedat P, Delansorne R, Daviet L. Small-molecule inhibitor
of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol
Cancer Ther. 2009 Aug;8(8):2286-95. doi: 10.1158/1535-7163.MCT-09-0097. Epub 2009
Aug 11. PubMed PMID: 19671755.
3: Lee KW, Cho JG, Kim CM, Kang AY, Kim M, Ahn BY, Chung SS, Lim KH, Baek KH,
Sung JH, Park KS, Park SG. Herpesvirus-associated ubiquitin-specific protease
(HAUSP) modulates peroxisome proliferator-activated receptor γ (PPARγ) stability
through its deubiquitinating activity. J Biol Chem. 2013 Nov 15;288(46):32886-96.
doi: 10.1074/jbc.M113.496331. Epub 2013 Sep 26. PubMed PMID: 24072712; PubMed
Central PMCID: PMC3829140.
