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AZD3965

AZD3965 ??? ???

?? ??:: 1448671-31-5

???:: AZD3965

???(??):: CS-2201;AZD-3965;AZD3965;AZD 3965;AZD3965,inhibit,Inhibitor,Monocarboxylate Transporter;(S)-5-(4-hydroxy-4-methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione;5-{[(4S)-4-Hydroxy-4-methyl-1,2-oxazolidin-2-yl]carbonyl}-1-isopropyl-3-methyl-6-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl}thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione;5-[[(4S)-4-Hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-3-methyl-1-(1-methylethyl)-6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione;Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, 5-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-3-methyl-1-(1-methylethyl)-6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-

CBNumber:: CB63034312

???:: C21H24F3N5O5S

??? ??:: 515.51

MOL ??:: 1448671-31-5.mol

?? ?? 77

AZD3965 ??

?? ?: 723.1±70.0 °C(Predicted)

??: 1.483±0.06 g/cm3(Predicted)

?? ??: Store at -20°C

???: insoluble in H2O; ≥51.5 mg/mL in DMSO; ≥51.6 mg/mL in EtOH

??? ??: ??? ??

?? ?? (pKa): 10.92±0.50(Predicted)

??: White to off-white

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?? ? ???? ?? (GHS)

????(GHS):

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Warning

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H320	?? ??? ???	?? ? ?? ?? ??? ??	?? 2B	??		P264, P305+P351+P338,P337+P313

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P337+P313	?? ?? ??? ???? ???? ??· ??? ????.

NFPA 704

	0
1		0

AZD3965 C??? ??, ??, ??

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AZD 3965 is a potent inhibitor of monocarboxylate transporter 1 (MCT1; K_i = 1.6 nM), killing tumor cells that are reliant on glycolysis by blocking lactate transport. It displays six-fold selectivity for MCT1 over MCT2 and is without effect against MCT4 at 10 μM. AZD 3965 increases intratumor lactate levels and decreases tumor growth in mice bearing COR-L103 small cell lung cancer (SCLC) xenografts. AZD 3965 also enhances radiosensitivity in mice with SCLC xenografts.

?? ???

This orally bioavailable MCT1 inhibitor (FW = 515.51 g/mol; CASs = 733809-45-5 and 1448671-31-5), also named (S) -5- (4-hydroxy-4- methylisoxazolidine-2-carbonyl) -1-isopropyl-3-methyl-6- ( (3-methyl-5- (tri- fluoromethyl) -1H-pyrazol-4-yl) methyl) -thieno[2,3-d]pyrimidine-2,4 (1H, 3H) -dione, selectively targets the Monocarboxylate Transporter-1 (IC50 = 1.6 nM) and is ~6x less active toward MCT2. AZD3965 does not inhibit MCT4, even at 10 μM. MCT1 and MCT4 are primarily involved in lactate transport, targeting highly glycolytic cancer cells, especially those that are hypoxic. The latter property suggests that the combined use with a vascular-disrupting anticancer agent (such as combrestatin) may improve the inhibitory action of AZD-3965 against cancer cells.

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