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Purity: ≥98%
KHS101 HCl, the hydrochloride salt of KHS-101, is a novel, selective and synthetic small-molecule inhibitor of transforming acidic coiled-coil protein 3 (TACC3) with potential anticancer activity. KHS101 promoted tumor cell death in diverse GBM (glioblastoma multiforme) cell models, independent of their tumor subtype, and without affecting the viability of noncancerous brain cell lines. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101 promoted aggregation of proteins regulating mitochondrial integrity and energy metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were selectively impaired in KHS101-treated GBM cells. In two intracranial patient-derived xenograft tumor models in mice, systemic administration of KHS101 reduced tumor growth and increased survival without discernible side effects. These findings suggest that targeting of HSPD1-dependent metabolic pathways might be an effective strategy for treating GBM.
| ln Vitro |
In adherent cultivated helper NPCs, KHS101 enhances neuronal evaporation in a dose-dependent manner (EC50=~1 μM). Under neurosphere-forming circumstances, KHS101 (1.5–5 μM) directs the production of neurons in the auxiliary hippocampus and secondary neurospheres produced from the subventricular zone (SVZ) that contain 40–60% TuJ1+ cells. Furthermore, compared to cells treated with vehicle [dimethylalkylene (DMSO)], hippocampus NPCs treated with KHS101 and attached to microelectrodes for 12 days showed neuronal morphology and spontaneous spiking KHS101 the proliferation of tumor cells. It has been demonstrated that TACC3, the neuroprogenitor KHS101, causes instability in TACC3-expressing cells, eventually lowering endogenous TACC3 protein levels [2].
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| ln Vivo |
Cell growth dramatically reduced (roughly increased) the tumors in KHS101-treated samples. Tumors treated with KHS101 exhibited higher levels of cell death (lower cellularity/higher pyknosis) in comparison to tumors treated with tumor vehicle controls. Treatment with KHS101 markedly inhibited vimentin-induced tumor growth of anterior to caudal GBM1 cells and around the corpus callosum. It was also discovered that the 10-week KHS101 treatment regimen markedly enhanced the mortality of rats with GBMX1 tumors (formed 2 or 6 weeks prior to treatment). Because of the treatment's side effects, no animals had to be taken out of the research. A noteworthy rise in animal mortality was also seen in another experiment employing consecutive KHS101 treatment regimen objectives in mice harboring GBMX1. A notable decrease in tumor size was observed in KHS101-treated mice, according to histological endpoint examination of animals treated with the drug and vehicle [2].
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| References |
[1]. Wurdak H, et al. A small molecule accelerates neuronal differentiation in the adult rat. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16542-7.
[2]. Polson ES, et al. KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice. Sci Transl Med. 2018 Aug 15;10(454). pii: eaar2718 |
| Molecular Formula |
C18H22CLN5S
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| Molecular Weight |
375.91
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| CAS # |
1784282-12-7
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| Related CAS # |
KHS101;1262770-73-9
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| SMILES |
CC(C)CNC1=NC(NCC2=CSC(C3=CC=CC=C3)=N2)=NC=C1.[H]Cl
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.67 mg/mL (7.10 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 26.7 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: ≥ 2.67 mg/mL (7.10 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 26.7 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: ≥ 2.67 mg/mL (7.10 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 | 2.6602 mL | 13.3011 mL | 26.6021 mL | |
| 5 mM | 0.5320 mL | 2.6602 mL | 5.3204 mL | |
| 10 mM | 0.2660 mL | 1.3301 mL | 2.6602 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.
KHS101 specifically induces neuronal differentiation in rat NPCs.Proc Natl Acad Sci U S A.2010 Sep 21;107(38):16542-7. |
Tacc3-specific shRNA recapitulates the neurogenic effect of KHS101 in rat NPCs.Proc Natl Acad Sci U S A.2010 Sep 21;107(38):16542-7. |
KHS101 significantly increases neuronal differentiation in rats in vivo.Proc Natl Acad Sci U S A.2010 Sep 21;107(38):16542-7. |
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