Related CAS #
2058116-52-0 (+); 2058116-54-2 (-)
Synonym
MDVN1003; MDVN-1003; MDVN 1003.
IUPAC/Chemical Name
1-(5-amino-2,3-dihydro-1H-inden-2-yl)-3-(8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
InChi Key
ULJLSBKQZMEISX-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H20FN7O/c23-16-8-13(9-17-20(16)31-4-3-26-17)19-18-21(25)27-10-28-22(18)30(29-19)15-6-11-1-2-14(24)5-12(11)7-15/h1-2,5,8-10,15,26H,3-4,6-7,24H2,(H2,25,27,28)
SMILES Code
NC1=C2C(N(C3CC(C=CC(N)=C4)=C4C3)N=C2C5=CC(NCCO6)=C6C(F)=C5)=NC=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:
MDVN1003 is a potent inhibitor of BTK amd PI3K delta.
In vitro activity:
This study discovered a single molecule, MDVN1003 (1-(5-amino-2,3-dihydro-1H-inden-2-yl)-3-(8-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine), that inhibits Bruton's tyrosine kinase and phosphatidylinositol-3-kinase δ, two proteins regulated by the B cell receptor that drive the growth of many NHLs. This dual inhibitor prevents the activation of B cells and inhibits the phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2, two downstream mediators that are important for this process.
Reference: J Pharmacol Exp Ther. 2017 May;361(2):312-321. https://pubmed.ncbi.nlm.nih.gov/28298527/
In vivo activity:
This orally bioavailable dual inhibitor (MDVN1003) reduced tumor growth in a B cell lymphoma mouse xenograft model more effectively than either ibrutinib or idelalisib. Taken together, these results suggest that dual inhibition of these two key pathways by a single molecule could be a viable approach for treatment of NHL patients.
Reference: J Pharmacol Exp Ther. 2017 May;361(2):312-321. https://pubmed.ncbi.nlm.nih.gov/28298527/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
417.45
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:
Alfaro J, Pérez de Arce F, Belmar S, Fuentealba G, Avila P, Ureta G, Flores C, Acuña C, Delgado L, Gaete D, Pujala B, Barde A, Nayak AK, Upendra TVR, Patel D, Chauhan S, Sharma VK, Kanno S, Almirez RG, Hung DT, Chakravarty S, Rai R, Bernales S, Quinn KP, Pham SM, McCullagh E. Dual Inhibition of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat Non-Hodgkin's B Cell Malignancies. J Pharmacol Exp Ther. 2017 May;361(2):312-321. doi: 10.1124/jpet.116.238022. Epub 2017 Mar 15. PMID: 28298527.
In vitro protocol:
Alfaro J, Pérez de Arce F, Belmar S, Fuentealba G, Avila P, Ureta G, Flores C, Acuña C, Delgado L, Gaete D, Pujala B, Barde A, Nayak AK, Upendra TVR, Patel D, Chauhan S, Sharma VK, Kanno S, Almirez RG, Hung DT, Chakravarty S, Rai R, Bernales S, Quinn KP, Pham SM, McCullagh E. Dual Inhibition of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat Non-Hodgkin's B Cell Malignancies. J Pharmacol Exp Ther. 2017 May;361(2):312-321. doi: 10.1124/jpet.116.238022. Epub 2017 Mar 15. PMID: 28298527.
In vivo protocol:
Alfaro J, Pérez de Arce F, Belmar S, Fuentealba G, Avila P, Ureta G, Flores C, Acuña C, Delgado L, Gaete D, Pujala B, Barde A, Nayak AK, Upendra TVR, Patel D, Chauhan S, Sharma VK, Kanno S, Almirez RG, Hung DT, Chakravarty S, Rai R, Bernales S, Quinn KP, Pham SM, McCullagh E. Dual Inhibition of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat Non-Hodgkin's B Cell Malignancies. J Pharmacol Exp Ther. 2017 May;361(2):312-321. doi: 10.1124/jpet.116.238022. Epub 2017 Mar 15. PMID: 28298527.
1: Alfaro J, Perez de Arce F, Belmar S, Fuentealba G, Avila P, Ureta G, Flores C, Acuna C, Delgado L, Gaete D, Pujala B, Barde A, Nayak AK, Upendra T, Patel D, Chauhan S, Sharma VK, Kanno S, Almirez RG, Hung DT, Chakravarty S, Rai R, Bernales S, Quinn KP, Pham SM, McCullagh E. Dual Inhibiton of Bruton's Tyrosine Kinase and Phosphoinositide-3-Kinase p110δ as a Therapeutic Approach to Treat non-Hodgkin's B cell Malignancies. J Pharmacol Exp Ther. 2017 Mar 15. pii: jpet.116.238022. doi: 10.1124/jpet.116.238022. [Epub ahead of print] PubMed PMID: 28298527.
