| Title |
CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia
|
|---|---|
| Published in |
Investigational New Drugs, September 2018
|
| DOI | 10.1007/s10637-018-0661-2 |
| Pubmed ID | |
| Authors |
Muhammed H. Rahaman, Yingyi Yu, Longjin Zhong, Julian Adams, Frankie Lam, Peng Li, Ben Noll, Robert Milne, Jun Peng, Shudong Wang |
| Abstract |
Acute myeloid leukemia (AML) is the most common form of acute leukemia with dismal long-term prognosis with age. The most aggressive subtype of AML is MLL-AML that is characterized by translocations of the mixed-lineage leukemia gene (MLL) and resistance to conventional chemotherapy. Cyclin dependent kinase 9 (CDK9) plays a crucial role in the MLL-driven oncogenic transcription, and hence, inhibiting activity of CDK9 has been proposed as a promising strategy for treatment of AML. We investigated the therapeutic potential of CDKI-73, one of the most potent CDK9 inhibitors, against a panel of AML cell lines and samples derived from 97 patients. CDKI-73 induced cancer cells undergoing apoptosis through transcriptional downregulation of anti-apoptotic proteins Bcl-2, Mcl-1 and XIAP by majorly targeting CDK9. Contrastively, it was relatively low toxic to the bone marrow cells of healthy donors. In MV4-11 xenograft mouse models, oral administration of CDKI-73 resulted in a marked inhibition of tumor growth (p < 0.0001) and prolongation of animal life span (P < 0.001) without causing body weight loss and other overt toxicities. The study suggests that CDKI-73 can be developed as a highly efficacious and orally deliverable therapeutic agent for treatment of AML. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 5 | 20% |
| Student > Bachelor | 4 | 16% |
| Researcher | 3 | 12% |
| Student > Ph. D. Student | 2 | 8% |
| Student > Doctoral Student | 1 | 4% |
| Other | 4 | 16% |
| Unknown | 6 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 20% |
| Nursing and Health Professions | 3 | 12% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Chemistry | 2 | 8% |
| Medicine and Dentistry | 2 | 8% |
| Other | 4 | 16% |
| Unknown | 7 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 September 2018.
All research outputs
#13,389,470
of 23,103,436 outputs
Outputs from Investigational New Drugs
#679
of 1,175 outputs
Outputs of similar age
#166,247
of 336,306 outputs
Outputs of similar age from Investigational New Drugs
#12
of 23 outputs
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So far Altmetric has tracked 1,175 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
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We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.