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ML-390 is an inhibitor of dihydroorotate dehydrogenase (DHODH), a key enzyme involved in the de novo pyrimidine synthesis pathway. It plays a crucial role in the regulation of cell proliferation and differentiation, particularly in acute myeloid leukemia (AML). By targeting DHODH, ML-390 effectively halts the development of leukemic myeloblasts at an immature stage, promoting their differentiation rather than self-renewal.
Used in Pharmaceutical Industry:
ML-390 is used as a therapeutic agent for the treatment of acute myeloid leukemia. It induces differentiation in AML cell lines, such as U937 (murine) and THP-1 (human), with an EC50 value of approximately 2 μM. This targeted approach offers a promising alternative to conventional chemotherapy, potentially reducing side effects and improving patient outcomes.
Used in Cancer Research:
ML-390 is used as a research tool for studying the mechanisms underlying the regulation of cell proliferation and differentiation in cancer cells. Its ability to inhibit DHODH and promote differentiation in AML cell lines makes it a valuable asset in understanding the complex interplay between genetic and epigenetic factors in cancer development and progression.
Used in Drug Development:
ML-390 serves as a lead compound in the development of novel therapeutic agents targeting DHODH and other enzymes involved in the de novo pyrimidine synthesis pathway. Its unique mechanism of action and potential efficacy against AML make it an attractive candidate for further optimization and drug development efforts.

2029049-79-2

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2029049-79-2 Usage

in vitro

in the screening study, ml390 was identified as the most potent compound against the engineered erhox-gfp cell line. moreover, the addition of uridine to the cell culture media could abrogate the differentiation effects of ml390, demonstrating further evidences that ml390’ effects were due to their inhibition of dhodh-catalyzed pyrimidine synthesis. in addition, ml390 was found to be not able to inhibit dhodh in the p. falciparum parasite, which is the causative agent of malaria. furthermore, the x-ray structure indicated that the binding of ml390 to the enzyme might be increased by modifying ml390 with a ring in its central portion to lock the molecule into its binding conformation with the amide substituents [1].

IC 50

0.56 μm

references

[1] timothy a lewis et al. development of ml390: a human dhodh inhibitor that induces differentiation in acute myeloid leukemia. acs med chem lett 2016 dec 28;7(12):1112-1117. epub 2016 sep 28.

Check Digit Verification of cas no

The CAS Registry Mumber 2029049-79-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 2,0,2,9,0,4 and 9 respectively; the second part has 2 digits, 7 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 2029049-79:
(9*2)+(8*0)+(7*2)+(6*9)+(5*0)+(4*4)+(3*9)+(2*7)+(1*9)=152
152 % 10 = 2
So 2029049-79-2 is a valid CAS Registry Number.

2029049-79-2Downstream Products

2029049-79-2Relevant academic research and scientific papers

COMPOUNDS AND METHODS USEFUL FOR TREATING OR PREVENTING HEMATOLOGICAL CANCERS

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Page/Page column 53; 54, (2017/03/28)

The present invention includes methods of treating patients with acute myeloid leukemia across a range of genetic subtypes with DHODH inhibitors, such as 6-fluoro-2-(2'-fluoro-[1,1'- biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid).

Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia

Sykes, David B.,Kfoury, Youmna S.,Mercier, Fran?ois E.,Wawer, Mathias J.,Law, Jason M.,Haynes, Mark K.,Lewis, Timothy A.,Schajnovitz, Amir,Jain, Esha,Lee, Dongjun,Meyer, Hanna,Pierce, Kerry A.,Tolliday, Nicola J.,Waller, Anna,Ferrara, Steven J.,Eheim, Ashley L.,Stoeckigt, Detlef,Maxcy, Katrina L.,Cobert, Julien M.,Bachand, Jacqueline,Szekely, Brian A.,Mukherjee, Siddhartha,Sklar, Larry A.,Kotz, Joanne D.,Clish, Clary B.,Sadreyev, Ruslan I.,Clemons, Paul A.,Janzer, Andreas,Schreiber, Stuart L.,Scadden, David T.

, p. 171 - 15,186 (2016/09/28)

While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a power

Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia

Lewis, Timothy A.,Sykes, David B.,Law, Jason M.,Mu?oz, Benito,Rustiguel, Joane K.,Nonato, Maria Cristina,Scadden, David T.,Schreiber, Stuart L.

supporting information, p. 1112 - 1117 (2016/12/16)

Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derive

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