Synonym
SJB3-019A; SJB3-019A; SJB3-019A; SJB 019; SJB019; SJB-019;
IUPAC/Chemical Name
2-(pyridin-3-yl)naphtho[2,3-d]oxazole-4,9-dione
InChi Key
DOYPPVCQHGJUBC-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H8N2O3/c19-13-10-5-1-2-6-11(10)14(20)15-12(13)18-16(21-15)9-4-3-7-17-8-9/h1-8H
SMILES Code
O=C(C1=C2OC(C3=CC=CN=C3)=N1)C4=C(C=CC=C4)C2=O
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
>3 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
More Info
The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma. Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in multiple myeloma biology is not defined.
Biological target:
SJB3-019A is 5 times more potent than SJB2-043 in promoting ID1 degradation and cytoxicity in K562 cells (IC50 = 0.0781 μM).
In vitro activity:
USP1 inhibitors, such as SJB3-019A, either alone or in combination, have potential in the treatment of multiple myeloma. SJB3-019A demonstrated efficacy in decreasing cell viability, overcoming bortezomib resistance, and inducing apoptosis in myeloma cells. It also disrupted DNA repair processes and downregulated key proteins associated with myeloma stem cell renewal. Combination studies with SJB3-019A and other therapeutic agents showed synergistic cytotoxicity.
Reference: Clin Cancer Res. 2017 Aug 1;23(15):4280-4289. https://pubmed.ncbi.nlm.nih.gov/28270494/
In vivo activity:
Genetic or pharmacological inhibition of USP1 restored the sensitivity of hepatocellular carcinoma cells to doxorubicin, representing a new potential therapeutic strategy for hepatocellular carcinoma. The combination of doxorubicin and SJB3-019A induced tumor inhibition in a xenograft and orthotopic liver tumor model.
Reference: Anticancer Drugs. 2022 Aug 1;33(7):622-631. https://pubmed.ncbi.nlm.nih.gov/35324534/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
10.0 |
36.20 |
|
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
276.25
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. Kuang X, Xiong J, Lu T, Wang W, Zhang Z, Wang J. Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells. Int J Med Sci. 2021 Jan 1;18(1):245-255. doi: 10.7150/ijms.47597. PMID: 33390793; PMCID: PMC7738972.
2. Das DS, Das A, Ray A, Song Y, Samur MK, Munshi NC, Chauhan D, Anderson KC. Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells. Clin Cancer Res. 2017 Aug 1;23(15):4280-4289. doi: 10.1158/1078-0432.CCR-16-2692. Epub 2017 Mar 7. PMID: 28270494; PMCID: PMC5540781.
3. Hao F, Li Y, Zhang Y, Han Y, Shang J, Gan L, Zheng J, Zhang C. Inhibition of USP1 ameliorates hypertensive nephropathy through regulating oxidative stress and ferroptosis: A precise treatment via SJB3-019A nanodelivery. Eur J Pharm Biopharm. 2023 Dec;193:187-197. doi: 10.1016/j.ejpb.2023.11.009. Epub 2023 Nov 9. PMID: 37949326.
4. Lu Z, Zhang Z, Yang M, Xiao M. Ubiquitin-specific protease 1 inhibition sensitizes hepatocellular carcinoma cells to doxorubicin by ubiquitinated proliferating cell nuclear antigen-mediated attenuation of stemness. Anticancer Drugs. 2022 Aug 1;33(7):622-631. doi: 10.1097/CAD.0000000000001311. Epub 2022 Mar 23. PMID: 35324534.
In vitro protocol:
1. Kuang X, Xiong J, Lu T, Wang W, Zhang Z, Wang J. Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells. Int J Med Sci. 2021 Jan 1;18(1):245-255. doi: 10.7150/ijms.47597. PMID: 33390793; PMCID: PMC7738972.
2. Das DS, Das A, Ray A, Song Y, Samur MK, Munshi NC, Chauhan D, Anderson KC. Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells. Clin Cancer Res. 2017 Aug 1;23(15):4280-4289. doi: 10.1158/1078-0432.CCR-16-2692. Epub 2017 Mar 7. PMID: 28270494; PMCID: PMC5540781.
In vivo protocol:
1. Hao F, Li Y, Zhang Y, Han Y, Shang J, Gan L, Zheng J, Zhang C. Inhibition of USP1 ameliorates hypertensive nephropathy through regulating oxidative stress and ferroptosis: A precise treatment via SJB3-019A nanodelivery. Eur J Pharm Biopharm. 2023 Dec;193:187-197. doi: 10.1016/j.ejpb.2023.11.009. Epub 2023 Nov 9. PMID: 37949326.
2. Lu Z, Zhang Z, Yang M, Xiao M. Ubiquitin-specific protease 1 inhibition sensitizes hepatocellular carcinoma cells to doxorubicin by ubiquitinated proliferating cell nuclear antigen-mediated attenuation of stemness. Anticancer Drugs. 2022 Aug 1;33(7):622-631. doi: 10.1097/CAD.0000000000001311. Epub 2022 Mar 23. PMID: 35324534.
1: Das DS, Das A, Ray A, Song Y, Samur MK, Munshi NC, Chauhan D, Anderson KC. Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells. Clin Cancer Res. 2017 Aug 1;23(15):4280-4289. doi: 10.1158/1078-0432.CCR-16-2692. Epub 2017 Mar 7. PubMed PMID: 28270494; PubMed Central PMCID: PMC5540781.
2: Kuang X, Xiong J, Lu T, Wang W, Zhang Z, Wang J. Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells. Int J Med Sci. 2021 Jan 1;18(1):245-255. doi: 10.7150/ijms.47597. PMID: 33390793; PMCID: PMC7738972.
3: Lu Z, Zhang Z, Yang M, Xiao M. Ubiquitin-specific protease 1 inhibition sensitizes hepatocellular carcinoma cells to doxorubicin by ubiquitinated proliferating cell nuclear antigen-mediated attenuation of stemness. Anticancer Drugs. 2022 Aug 1;33(7):622-631. doi: 10.1097/CAD.0000000000001311. Epub 2022 Mar 23. PMID: 35324534.Hao F, Li Y, Zhang Y, Han Y, Shang J, Gan L, Zheng J, Zhang C.
4: Hao F, Li Y, Zhang Y, Han Y, Shang J, Gan L, Zheng J, Zhang C. Inhibition of USP1 ameliorates hypertensive nephropathy through regulating oxidative stress and ferroptosis: A precise treatment via SJB3-019A nanodelivery. Eur J Pharm Biopharm. 2023 Dec;193:187-197. doi: 10.1016/j.ejpb.2023.11.009. Epub 2023 Nov 9. PMID: 37949326.
