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| 25mg |
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| Targets |
KA-2507 targets HDAC6 (histone deacetylase 6), a class IIb histone deacetylase that deacetylates non-histone proteins including α-tubulin and Hsp90. HDAC6 plays a role in regulating cellular processes including protein degradation, cytoskeletal dynamics, and stress responses. By inhibiting HDAC6 with high potency (IC50 = 2.5 nM), KA-2507 disrupts HDAC6-mediated deacetylation, leading to antitumor effects and immune modulation.
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| ln Vitro |
In vitro growth of human or mouse cancer cells is not inhibited by KA2507 at dosages that specifically block HDAC6 [1].
In vitro, KA-2507 is a potent and selective HDAC6 inhibitor with an IC50 of 2.5 nM. It binds to and inhibits the activity of HDAC6. The compound's potent and selective HDAC6 inhibition makes it valuable for studying the role of HDAC6 in cancer, immune regulation, and protein homeostasis. However, specific cellular activity data have not been detailed in the available literature. |
| ln Vivo |
KA2507 (100-200 mg/kg; oral; daily; for 20 days) suppresses tumor growth in the syngeneic B16-F10 mouse melanoma model [1]. KA2507 has shown anti-tumor activity in CT26 and MC38 colorectal cancer models [1]. Analysis of tumor samples also demonstrated modulation of anti-tumor immune biomarkers at effective doses, with KA2507 administration leading to reduced activation of STAT3 (measured by phosphorylated STAT3, an important suppressor of anti-tumor immune responses), reduced PD-L1 expression, decreased PD- L1 expression increases MHC class I expression [1]. KA2507 has poor oral bioavailability (15% in mice) and Cmax (300 ng/mL in mice) after oral treatment (200 mg/kg in mice) [1].
In vivo, KA-2507 (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in a syngeneic B16-F10 mouse melanoma model. It also shows antitumor effects in CT26 and MC38 colorectal cancer models. Tumor sample analysis suggests immune modulatory effects. The compound's oral bioavailability and in vivo efficacy support its potential for cancer research and immunotherapy. |
| Enzyme Assay |
For in vitro enzyme assays, recombinant HDAC6 protein is incubated with a fluorogenic substrate (such as a acetylated peptide) in assay buffer. The test compound is added at various concentrations (0.1-1000 nM). Deacetylase activity is measured by monitoring fluorescence over time. IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, cancer cells are treated with KA-2507 at concentrations ranging from 0.1-10 µM. HDAC6 activity is assessed by measuring α-tubulin acetylation levels by Western blotting. Cell viability and proliferation are measured using MTT or CellTiter-Glo assays. Immune cell function can be assessed by measuring cytokine production and T cell activation.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mouse, B16-F10 melanoma model [1]
Doses: 100 mg/kg, 200 mg/kg, 200 mg/kg Route of Administration: po (oral gavage), daily, for 20 days Experimental Results: Shows anti-tumor efficacy. Animal/Disease Models: Male C57BL/6 mice [1] Doses: 200 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral Experimental Results: Oral bioavailability (15%), Cmax (300 ng/mL). For in vivo efficacy studies, syngeneic mouse models (B16-F10 melanoma, CT26, or MC38 colorectal cancer) are used. KA-2507 is administered orally at doses of 100-200 mg/kg daily for 20 days. Tumor volumes are measured twice weekly. At study endpoint, tumors are collected for analysis of HDAC6 inhibition, immune cell infiltration, and antitumor immune responses. |
| ADME/Pharmacokinetics |
KA-2507 is orally bioavailable. It is soluble in DMSO (66.67 mg/mL, 206.84 mM). Storage is recommended at 4°C protected from light. Further detailed PK parameters including half-life, Cmax, AUC, and tissue distribution would be available from the primary literature. The compound is for research use only.
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| Toxicity/Toxicokinetics |
Toxicological data for KA-2507 would be available from preclinical studies. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
KA2507, an HDAC6 inhibitor, is an orally bioavailable histone deacetylase type 6 (HDAC6; HDAC-6) inhibitor with potential antitumor activity. After administration, KA2507 targets and binds to HDAC6, inhibiting its activity. This leads to the accumulation of highly acetylated chromatin histones, inducing chromatin remodeling and altering gene expression patterns. Specifically, inhibition of HDAC6 blocks STAT3 activity, thereby reducing the expression of programmed death receptor 1 (PD-1). Ultimately, this results in selective transcription of tumor suppressor genes, tumor suppressor protein-mediated inhibition of tumor cell division, and induction of apoptosis in HDAC6-overexpressing tumor cells. HDAC6 is highly expressed in various tumor cell types, and its function is to deacetylate chromatin histones.
KA-2507 is a potent and selective HDAC6 inhibitor with an IC50 of 2.5 nM. It is orally bioavailable with potential antineoplastic activity. KA-2507 (100-200 mg/kg; p.o.) inhibits tumor growth in melanoma and colorectal cancer models. It is a research tool and is not approved for clinical use. |
| Molecular Formula |
C16H14N6O2
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|---|---|
| Molecular Weight |
322.321362018585
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| Exact Mass |
322.117
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| CAS # |
1636894-46-6
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| Related CAS # |
KA2507 monohydrochloride;2972712-63-1
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| PubChem CID |
117703516
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| Appearance |
White to light brown solid powder
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| LogP |
0.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
384
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CC(=CC=1)CN(C1C=NC=CN=1)C1C=NC=CN=1)NO
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| InChi Key |
LXHMTDHBMRZSHJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H14N6O2/c23-16(21-24)13-3-1-12(2-4-13)11-22(14-9-17-5-7-19-14)15-10-18-6-8-20-15/h1-10,24H,11H2,(H,21,23)
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| Chemical Name |
4-[[di(pyrazin-2-yl)amino]methyl]-N-hydroxybenzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~66.67 mg/mL (~206.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1025 mL | 15.5125 mL | 31.0251 mL | |
| 5 mM | 0.6205 mL | 3.1025 mL | 6.2050 mL | |
| 10 mM | 0.3103 mL | 1.5513 mL | 3.1025 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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