2. Protein Tyrosine Kinase/RTK Apoptosis
  3. Anaplastic lymphoma kinase (ALK) Apoptosis
  4. DDO-2728

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.

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DDO-2728 Chemical Structure

DDO-2728 Chemical Structure

CAS No. : 3029515-97-4

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5 mg USD 570 In-stock
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Based on 1 publication(s) in Google Scholar

DDO-2728 Related Antibodies

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Description

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].

IC50 & Target

AlkB homologue 5 (ALKBH5) IC50: 2.97 μM[1]
In Vitro

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

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

DDO-2728 Related Antibodies

Cell Proliferation Assay[1]

Cell Line: MOLM-13, MV4-11, HEK293, HUVEC
Concentration: 0.01-100 μM
Incubation Time: 72 h
Result: Inhibited the proliferation of MOLM-13 and MV4−11 cells with IC50s of 0.45 and 1.2 μM respectively, didn't show visual cytotoxicity in HEK293 and HUVECs under 1 μM.

Apoptosis Analysis[1]

Cell Line: MOLM-13, MV4-11
Concentration: 0, 5, 10 μM
Incubation Time: 48 h
Result: Induced cell apoptosis of MV4−11 and MOLM-13 cells concentration-dependently, apoptosis rate for MV4−11 increased from 7.17% to 55.4%, apoptosis rate for MOLM-13 increased from 6.49% to 31.5%.

Cell Cycle Analysis[1]

Cell Line: MOLM-13, MV4-11
Concentration: 20 μM
Incubation Time: 48 h
Result: Arrested the cell cycle of MOLM-13 and MV4−11 cells at the G1/M phase as no G2/M phase cells exist.
In Vivo

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

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: MV4−11 xenograft nude mice [1]
Dosage: 10, 20, and 40 mg/kg
Administration: Intraperitoneal injection (i.p.) daily for 14 d
Result: Inhibited tumor growth significantly even at a concentration of 10 mg/kg. No significant change in the weight of the mice and the main organs during the treatment, the organ weight of test group mice was the same as vehicle group, no obvious injury damage was observed in the HE staining images of organ tissues.
Molecular Weight

578.45

Formula

C28H17F3N4O7
CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

OC1=C(C(O)=C(C=C1)[N+]([O-])=O)C(C(C=N2)=CN3C2=CC(C4=CC=C(C=C4)C(OCC5=CC=C(C=C5)C(F)(F)F)=O)=N3)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 125 mg/mL (216.09 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7288 mL 8.6438 mL 17.2876 mL
5 mM 0.3458 mL 1.7288 mL 3.4575 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.7288 mL 8.6438 mL 17.2876 mL 43.2189 mL
5 mM 0.3458 mL 1.7288 mL 3.4575 mL 8.6438 mL
10 mM 0.1729 mL 0.8644 mL 1.7288 mL 4.3219 mL
15 mM 0.1153 mL 0.5763 mL 1.1525 mL 2.8813 mL
20 mM 0.0864 mL 0.4322 mL 0.8644 mL 2.1609 mL
25 mM 0.0692 mL 0.3458 mL 0.6915 mL 1.7288 mL
30 mM 0.0576 mL 0.2881 mL 0.5763 mL 1.4406 mL
40 mM 0.0432 mL 0.2161 mL 0.4322 mL 1.0805 mL
50 mM 0.0346 mL 0.1729 mL 0.3458 mL 0.8644 mL
60 mM 0.0288 mL 0.1441 mL 0.2881 mL 0.7203 mL
80 mM 0.0216 mL 0.1080 mL 0.2161 mL 0.5402 mL
100 mM 0.0173 mL 0.0864 mL 0.1729 mL 0.4322 mL
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DDO-2728 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

DDO-27283029515-97-4DDO2728DDO 2728Anaplastic lymphoma kinase (ALK)ApoptosisAnaplastic lymphoma kinaseALK tyrosine kinase receptorCD246Cluster of differentiation 246MV4?11MOLM-13HEK293HUVECSD ratsnude miceALKBH5 inhibitorm6Acell apoptosiscycle arrestcanceracute myeloid leukemiaInhibitorinhibitorinhibit

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