DDO-2728

• CAT Number: I040220
• CAS Number: 3029515-97-4
• Molecular Formula: C28H17F3N4O7
• Molecular Weight: 578.45
• Purity: ≥95%
• Synonyms: [4-(trifluoromethyl)phenyl]methyl 4-[6-(2,6-dihydroxy-3-nitrobenzoyl)pyrazolo[1,5-a]pyrimidin-2-yl]benzoate
• InChI: InChI=1S/C28H17F3N4O7/c29-28(30,31)19-7-1-15(2-8-19)14-42-27(39)17-5-3-16(4-6-17)20-11-23-32-12-18(13-34(23)33-20)25(37)24-22(36)10-9-21(26(24)38)35(40)41/h1-13,36,38H,14H2
• InChIKey: VIQXHWIGOQADLR-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1COC(=O)C2=CC=C(C=C2)C3=NN4C=C(C=NC4=C3)C(=O)C5=C(C=CC(=C5O)[N+](=O)[O-])O)C(F)(F)F

DDO-2728 (compound 19) is a selective AlkB homologue 5 (ALKBH5) inhibitor with an IC50 of 2.97 μM. DDO-2728 increases the abundance of N6 methyladenosine (m6A) modifications, inducing cell apoptosis and cycle arrest. DDO-2728 suppresses tumor growth in the MV4−11 xenograft model with favorable safety profile, shows the potential of targeting ALKBH5 in cancer research[1].
DDO-2728 (0-40 μM, 48 h) increases m6A methylation levels in the MOLM-13, HEK293and MV4−11 cells over a concentration gradient[1].
DDO-2728 (0.01-100 μM, 72 h) inhibits the proliferation of MOLM-13 and MV4−11 cells with IC50s of 0.45 and 1.2 μM respectively, and showes a relatively weak toxicity in HEK293 and HUVECs[1].
DDO-2728 (20 μM, 48 h) significantly arrests the cell cycle of MOLM-13 and MV4−11 cells at the G1/M phase[1].
DDO-2728 (5, 10 μM, 48 h) concentration-dependently induces cell apoptosis of MV4−11 and MOLM-13 cells[1].
DDO-2728 (20 μM, 24 h) decreases the half-lives of TACC3 mRNA in MOLM-13 and MV4−11 cells[1].
DDO-2728 (0-10 μM, 48 h) significantly reduces the abundance of TACC3 and c-Myc in MOLM-13 and MV4−11 cells at both mRNA and protein levels[1].

1.19

Metabolic Stability in Rat and Human Plasma and Liver Microsomes[1]

Species
Plasma T1/2 (min)
Microsome T1/2 (min)
Microsome CL (μL/min/mg)

Human
624
430
3.2

Rat
251
13.8
100.4
DDO-2728 (10-40 mg/kg, i.p., daily for 14 d) effectively inhibits tumor growth in MV4−11 xenograft nude mice.[1].

1.19

Pharmacokinetic Parameters of DDO-2728 in Rats[1]

Parameter
Rat (i.v., 2mg/kg)
Rat (i.p., 10mg/kg)

T1/2 (min)
36.7 ± 3.2
148.3 ± 4.6

Cmax (ng/mL)
13388.3 ± 784.5
2337.5 ± 295.7

Tmax (min)

30

AUC0-∞ (min·μg/mL)
404.3 ± 58.6
349.1 ± 26.1

Vz_F_obs (mL/kg)
263.6 ± 17.5
6177.6 ± 650.2

Cl_F_obs (mL/min/kg)
5.0 ± 0.5
28.8 ± 2.2

MRT (min)
77.8 ± 15.5
168.2 ± 1.2

F (%)

17.3

Reference

[1]. Zheng-Yu Jiang, et al. Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Novel and Selective ALKBH5 Inhibitor for the Treatment of AML. Journal of Medicinal Chemistry. 2023，Article ASAP.
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