| Identification | Back Directory | [Name]
CB 3717 | [CAS]
76849-19-9 | [Synonyms]
PDDF
CB 3717
8-dideazafolic acid
N(sup 10)-Propargyl-5
LTKHPMDRMUCUEB-IBGZPJMESA-N
10-Propargyl-5,8-dideazafolate
10-Propargyl-5,8-dideazafolic acid
N(sup 10)-Propargyl-5,8-dideazafolic acid
N10)-PROPARGYL-5,8-DIDEAZAFOLIC ACID
N-[p-[Propargyl(2-amino-4-hydroxyquinazolin-6-ylmethyl)amino]benzoyl]-L-glutamic acid
N-[4-[[(2-Amino-1,4-dihydro-4-oxoquinazolin-6-yl)methyl]-2-propynylamino]benzoyl]-L-glutamic acid
L-Glutamic acid, N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-quinazolinyl)methyl]-2-propyn-1-ylamino]benzoyl]- | [Molecular Formula]
C24H23N5O6 | [MDL Number]
MFCD00869489 | [MOL File]
76849-19-9.mol | [Molecular Weight]
477.475 |
| Hazard Information | Back Directory | [Hazard]
A poison.
| [Description]
CB 3717, a potent inhibitor of
thymidylate synthase, is toxic for cell lines with
altered dihydrofolate reductase; and homofolate, a de novo purine inhibitor requiring dihydrofolate reductase for activation, is effective
in reductase-amplified lines. | [Uses]
CB 3717 is a potent inhibitor of human thymidylate synthetase, competitively binding with 5,10-methylenetetrahydrofolate (Ki = 4.9 X 10(-9) M). It also competitively inhibits human dihydrofolate reductase with dihydrofolate (Ki = 2.3 X 10(-8) M). In WI-L2 human lymphoblastoid cells, CB 3717 treatment led to a significant decrease in cellular dTTP levels and a notable increase in dUMP levels, indicating a disruption in nucleotide metabolism. The growth-inhibitory effect of CB 3717 was reversed by thymidine supplementation, demonstrating that thymidylate synthetase became rate-limiting in the presence of this compound. Delayed thymidine supplementation beyond 8 hours resulted in severe cytotoxicity, underscoring the critical timing of nucleotide rescue strategies in CB 3717-treated cells[1]. | [Definition]
ChEBI: CB3717 is a N-acyl-L-glutamic acid. | [References]
[1] Biochemical effects of a quinazoline inhibitor of thymidylate synthetase, N-(4-(N-(( 2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino) benzoyl)-L-glutamic acid (CB3717), on human lymphoblastoid cells DOI:10.1016/0006-2952(83)90150-8 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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