Chemistry:CKD-506
CKD-506 is a histone deacetylase (HDAC) inhibitor which is under development for the treatment of inflammatory bowel diseases (IBDs) and rheumatoid arthritis.[1][2][3][4] It acts as a selective HDAC6 inhibitor.[1][2][4] The drug is taken orally.[1]
Pharmacology
| Enzyme | IC50 (nM) |
|---|---|
| HDAC1 | >2,000 |
| HDAC2 | >2,000 |
| HDAC3 | >2,000 |
| HDAC4 | >2,000 |
| HDAC5 | >2,000 |
| HDAC6 | ~5 |
| HDAC7 | >2,000 |
| HDAC8 | >2,000 |
| HDAC9 | >2,000 |
| HDAC10 | >2,000 |
| HDAC11 | >2,000 |
| Refs: [4] | |
CKD-506 is a selective HDAC6 inhibitor, with an IC50 of around 5 nM.[4] It showed greater than 100-fold selectivity for inhibition of HDAC6 over other HDACs, with IC50 values of 2,000 to 5,000 nM at HDAC1, HDAC2, HDAC7, and HDAC8 and no significant inhibition of other HDACs including HDAC3, HDAC4, HDAC5, HDAC9, HDAC10, and HDAC11.[4] The drug produces anti-inflammatory effects in animal models of autoimmune diseases such as multiple sclerosis (MS), systemic lupus erythematosus (SLE; lupus), and rheumatoid arthritis.[2][3][4] It also shows anti-inflammatory effects and enhances gut barrier function in animal models of inflammatory bowel disease.[5][6] The pharmacokinetics of CKD-506 in rodents have been described.[4]
Chemistry
The chemical structure of CKD-506 does not yet appear to have been disclosed.[1][7][2]
History and development
CKD-506 was first described in the scientific literature by 2017.[8][9][4][2] It was developed by Chong Kun Dang Pharmaceutical.[1] As of August 2022, the drug is in phase 2 clinical trials for both inflammatory bowel diseases and rheumatoid arthritis.[1]
See also
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "CKD 506". 31 August 2022. https://adisinsight.springer.com/drugs/800050914.
- ↑ 2.0 2.1 2.2 2.3 2.4 "CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis". Scientific Reports 11 (1). July 2021. doi:10.1038/s41598-021-93232-6. PMID 34262061. Bibcode: 2021NatSR..1114466B.
- ↑ 3.0 3.1 "Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis". Arthritis Research & Therapy 22 (1). July 2020. doi:10.1186/s13075-020-02258-0. PMID 32711562.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 "CKD-506, a novel HDAC6-selective inhibitor, improves renal outcomes and survival in a mouse model of systemic lupus erythematosus". Scientific Reports 8 (1). November 2018. doi:10.1038/s41598-018-35602-1. PMID 30470828. Bibcode: 2018NatSR...817297C.
- ↑ "Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function". Gut and Liver 17 (5): 766–776. September 2023. doi:10.5009/gnl220159. PMID 36167345.
- ↑ "Novel Histone Deacetylase 6 Inhibitor CKD-506 Inhibits NF-κB Signaling in Intestinal Epithelial Cells and Macrophages and Ameliorates Acute and Chronic Murine Colitis". Inflammatory Bowel Diseases 26 (6): 852–862. May 2020. doi:10.1093/ibd/izz317. PMID 31895948.
- ↑ "Novel Selective Histone Deacetylase 6 (HDAC6) Inhibitors: A Patent Review (2016-2019)". Recent Patents on Anti-Cancer Drug Discovery 15 (1): 32–48. 2020. doi:10.2174/1574892815666200217125419. PMID 32065106. "To the time of publication of this paper, the structure of CKD-506 has not been disclosed. According to Chong Kun Dang’s press release, the patent covering CKD506 was granted in Korea in July 2016, and it was filed in fifty-three countries in April 2014 [86]. [...] 3.3. CKD-506 (Structure has not been disclosed) [...]".
- ↑ "CKD-506, a Novel Inhibitor of Histone Deacetylase 6 (HDAC6) Has a Therapeutic Potential in Rheumatoid Arthritis and Inflammatory Bowel Disease.". Arthritis & Rheumatology. 69. Hoboken, NJ: Wiley. October 2017.
- ↑ "Safety, tolerability, pharmacokinetics and pharmacodynamics of CKD-506, a novel, Histone Deacetylase 6 (HDAC6) inhibitor, in healthy volunteers". 2018 ACR/ARHP Annual Meeting. ACR. October 2018. https://scholar.google.com/scholar?cluster=1925238706765153150.
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