WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205800
CAS#: 910462-43-0
Description: Domatinostat, also known as 4SC-202, is an orally bioavailable benzamide and inhibitor of human class I histone deacetylases (HDACs) isoenzymes 1, 2 and 3, with potential antineoplastic activity. HDAC inhibitor 4SC-202 selectively binds to and inhibits class I HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, the selective transcription of tumor suppressor genes, and the tumor suppressor protein-mediated inhibition of tumor cell division and eventually the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins.
MedKoo Cat#: 205800
Name: 4SC-202
CAS#: 910462-43-0
Chemical Formula: C23H21N5O3S
Exact Mass: 447.13651
Molecular Weight: 447.51
Elemental Analysis: C, 61.73; H, 4.73; N, 15.65; O, 10.73; S, 7.17
Synonym: 4SC202; 4SC-202; 4SC 202; domatinostat;
IUPAC/Chemical Name: (E)-N-(2-aminophenyl)-3-(1-((4-(1-methyl-1H-pyrazol-4-yl)phenyl)sulfonyl)-1H-pyrrol-3-yl)acrylamide.
InChi Key: IAVXAZDVNICKFJ-ICSBZGNSSA-N
InChi Code: InChI=1S/C23H21N5O3S.C7H8O3S/c1-27-16-19(14-25-27)18-7-9-20(10-8-18)32(30,31)28-13-12-17(15-28)6-11-23(29)26-22-5-3-2-4-21(22)24;1-6-2-4-7(5-3-6)11(8,9)10/h2-16H,24H2,1H3,(H,26,29);2-5H,1H3,(H,8,9,10)/b11-6+;
SMILES Code: O=C(NC1=CC=CC=C1N)/C=C/C2=CN(S(=O)(C3=CC=C(C4=CN(C)N=C4)C=C3)=O)C=C2.O=S(C5=CC=C(C)C=C5)(O)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Domatinostat (4SC-202) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Also displays inhibitory activity against Lysine specific demethylase 1 (LSD1). |
| In vitro activity: | Histone deacetylase (HDAC) overactivity in colorectal cancer (CRC) promotes cancer progression. In the current study, it was shown that 4SC-202, a novel class I HDAC inhibitor (HDACi), potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). Yet, the same 4SC-202 treatment was non-cytotoxic to colon epithelial cells where HDAC-1/-2 expressions were extremely low. 4SC-202 provoked apoptosis activation in CRC cells, while caspase inhibitors (z-VAD-CHO and z-DVED-CHO) significantly alleviated 4SC-202-exerted cytotoxicity in CRC cells. Meanwhile, 4SC-202 induced dramatic G2-M arrest in CRC cells. Further studies showed that AKT activation might be an important resistance factor of 4SC-202. 4SC-202-induced cytotoxicity was dramatically potentiated with serum starvation, AKT inhibition (by perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. On the other hand, exogenous expression of constitutively active AKT1 (CA-AKT1) decreased the sensitivity by 4SC-202 in HT-29 cells. Reference: Tumour Biol. 2016 Aug;37(8):10257-67. https://link.springer.com/article/10.1007/s13277-016-4868-6 |
| In vivo activity: | SKM-1 cells transfected with LV-HO-1 and its empty vector (EV) were injected to the tail vein of NOD/SCID mice. After confirming successful engraftment in these recipient mice at 14 days after transplantation, 4SC-202 was orally administered at a dose of 80 mg/kg/day for five consecutive days, followed by observation of the change in human CD45-positive cells by flow cytometry. As a result, after 2 weeks of 4SC-202 administration, the proportion of human CD34-positive cells were significantly decreased, and it was found that up-regulation of HO-1 accelerated cell proliferation and decreased the 4SC-202-inhibited MDS cell proliferation (Figure 5A, ,5B).5B). Meanwhile, observations were made for 130 days and recorded the death time of these mice, which was showed by aplan-Meier plot. The survival curve indicated that 4SC-202 effectively improved the survival of recipient mice, however, up-regulation of HO-1 delayed the time of 4SC-202-killing SKM-1 cells (Figure 5C). These results indicated that 4SC-202 effectively inhibited MDS cell proliferation and HO-1 influenced the inhibitory effects of 4SC-202 on SKM-1 cell proliferation in vivo. Reference: Am J Transl Res. 2020 Jun 15;12(6):2968-2983. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32655823/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 89.0 | 198.88 |
The following data is based on the product molecular weight 447.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Zhijun H, Shusheng W, Han M, Jianping L, Li-Sen Q, Dechun L. Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells. Tumour Biol. 2016 Aug;37(8):10257-67. doi: 10.1007/s13277-016-4868-6. Epub 2016 Feb 1. PMID: 26831668. 2. Fu M, Wan F, Li Z, Zhang F. 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2016 Mar 4;471(2):267-73. doi: 10.1016/j.bbrc.2016.01.030. Epub 2016 Jan 8. PMID: 26773495. 3. Wang W, Zhang Z, Kuang X, Ma D, Xiong J, Lu T, Zhang Y, Yu K, Zhang S, Wang J, Fang Q. 4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism. Am J Transl Res. 2020 Jun 15;12(6):2968-2983. PMID: 32655823; PMCID: PMC7344078. |
| In vitro protocol: | 1. Zhijun H, Shusheng W, Han M, Jianping L, Li-Sen Q, Dechun L. Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells. Tumour Biol. 2016 Aug;37(8):10257-67. doi: 10.1007/s13277-016-4868-6. Epub 2016 Feb 1. PMID: 26831668. 2. Fu M, Wan F, Li Z, Zhang F. 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2016 Mar 4;471(2):267-73. doi: 10.1016/j.bbrc.2016.01.030. Epub 2016 Jan 8. PMID: 26773495. |
| In vivo protocol: | 1. Wang W, Zhang Z, Kuang X, Ma D, Xiong J, Lu T, Zhang Y, Yu K, Zhang S, Wang J, Fang Q. 4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism. Am J Transl Res. 2020 Jun 15;12(6):2968-2983. PMID: 32655823; PMCID: PMC7344078. |
4SC-202 is an orally administered selective class I HDAC inhibitor. 4SC-202 demonstrates a particularly strong anti-mitotic activity. 4SC-202 enables a dual attack on malignant cancer cells and is therefore not a back-up compound for resminostat. Its strong, specific anti-mitotic effect could make this candidate particularly suitable for the treatment of cancer types that exhibit high rates of cell division. 4SC-202, currently being developed by A German Company called 4SC, is in the Phase I TOPAS study in order to evaluate the safety, pharmacokinetics and clinical efficacy of the orally administered compound in patients with advanced hematological indications, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic syndrome (MDS) and lymphomas (source: http://www.4sc.de/product-pipeline/clinical/4SC-202).
