KHS101 hydrochloride

KHS101 is a blood-brain barrier-penetrant anticancer agent that primarily functions by inhibiting HSPD1 (IC₅₀ = 14.4 μM) and TACC3 across different cellular backgrounds. KHS101 promotes the aggregation of HSPD1 with client proteins, destabilizes TACC3, and reduces the levels of TACC3, Aurora A and PLK1. KHS101 induces autophagy, apoptosis, cell cycle exit and neuronal differentiation; it suppresses cancer cell growth, motility, EMT and stemness; it also impairs mitochondrial bioenergetics and glycolysis in glioblastoma cells. KHS101 can be used in research related to glioblastoma multiforme and breast cancer^[1][2][3]. IC50 & Target:TACC3^[1] In Vitro:KHS101 (0-20 μM; 5 days) induces dose-dependent cytotoxicity in all 6 patient-derived GBM cell lines as well as U251/U87 cells, with IC₅₀ values at 5 days of treatment as follows: 2.23 μM in GBM1 cells, 0.97 μM in GBM4 cells, 5.05 μM in GBM11 cells, 3.28 μM in GBM13 cells, 1.98 μM in GBM14 cells, and 1.87 μM in GBM20 cells^[1].
Treatment with KHS101 (1-7.5 μM; 12 h) selectively induces concentration-dependent autophagy in patient-derived human glioblastoma (GBM) cell lines (GBM1, GBM4, GBM11, GBM13, GBM14, GBM20), whereas no observable effect is detected in non-cancerous NP1 neural progenitor cells^[1].
KHS101 (7.5 μM; 48 h) selectively induces time-dependent apoptosis in patient-derived human GBM cell lines (GBM1, GBM11, GBM20), while exerting minimal effects on non-cancerous NP1 neural progenitor cells, and this apoptosis is independent of late-stage autophagy^[1].
KHS101 (7.5 μM) selectively disrupts the metabolic phenotype of patient-derived human GBM cell lines and induces a significant hypoxic shift in metabolic activity, whereas acute treatment at 7.5 μM causes only minimal glycolytic changes in non-cancerous cell lines (NP1, NP2, NHAs)^[1].
KHS101 (7.5 μM; 4-24 h) selectively impairs aerobic glycolysis and tricarboxylic acid (TCA) cycle activity in patient-derived human GBM1 cells, reduces the incorporation of glucose-derived carbon into key metabolic intermediates, and decreases total cellular ATP levels by ≥ 50% after 24 hours; this agent exerts no such effects in non-cancerous NP1 neural progenitor cells^[1].
KHS101 (7.5 μM; 1 h) selectively induces the aggregation of HSPD1 and key metabolic enzymes in patient-derived human GBM1 cells, whereas only minimal aggregation is observed in non-cancerous NP1 neural progenitor cells^[1].
KHS101 (10-100 μM; 24 h) inhibits the proliferation of MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells in a TACC3 expression-dependent manner, with 20 μM selectively suppressing the growth of breast cancer cells without affecting the non-tumorigenic mammary epithelial cell line MCF10A^[2].
KHS101 (5-20 μM; 24 h) reduces TACC3 protein levels in MDA-MB-231 and SKBR3 breast cancer cells at the concentration of 20 μM, but does not alter TACC3 levels in MDA-MB-468 and BT549 breast cancer cells after 24 h of treatment^[2].
KHS101 (5-20 μM; 7 days) inhibits mammosphere formation and reduces mammosphere formation efficiency in MDA-MB-468 and SKBR3 breast cancer cells^[2].
KHS101 (5-20 μM; 24 h) reduces the mRNA expression levels of the stem cell markers Oct4, Sox2 and Nanog in MDA-MB-231 breast cancer cells^[2].
KHS101 (20 μM; 24 h) reduces the protein expression levels of mesenchymal markers (N-cadherin, Vimentin) and the stemness marker CD44 in MDA-MB-231 breast cancer cells^[2].
KHS101 (20 μM; 24 h) reduces the mRNA expression levels of EMT transcription factors including Snail, Slug and Twist in MDA-MB-231 breast cancer cells^[2].
KHS101 (20-60 μM; 16 h) inhibits the migration of MDA-MB-231 and MDA-MB-468 breast cancer cells^[2].
KHS101 (20 μM; 24 h) inhibits the invasion of MDA-MB-231 and MDA-MB-468 breast cancer cells after treatment at 20 μM for 24 h^[2].
KHS101 (20 μM; 24-72 h) increases the sub-G1 phase apoptotic cell population in MDA-MB-231 and MDA-MB-468 breast cancer cells after treatment at 20 μM for 24, 48, and 72 h, and exerts cell type-specific effects on the overall cell cycle distribution^[2].
KHS101 (20 μM; 24-72 h) induces time-dependent apoptosis in MDA-MB-231 and MDA-MB-468 breast cancer cells after treatment at 20 μM for 24, 48, and 72 h, with a stronger effect on MDA-MB-468 cells^[2].
KHS101 (20 μM) alters the global proteomic profile of MDA-MB-468 breast cancer cells, with significant changes observed in proteins involved in catalytic activity, binding, metabolic processes, cellular processes, and multiple cancer-related signaling pathways^[2].
KHS101 (20 μM; 24 h) reduces the protein expression of Aurora A and PLK1 mitotic kinases in MDA-MB-468, SKBR3 and MCF7 breast cancer cells^[2].
KHS101 (0.6-5 μM; 1-12 d) induces neuronal differentiation of adherently cultured adult rat hippocampal neural progenitor cells (NPCs) in a dose-dependent manner, with an EC₅₀ of approximately 1 μM; treatment at 5 μM for 12 days generates functionally mature neurons^[3].
KHS101 (1.5-5 μM; 4 d) induces neuronal differentiation of secondary neurospheres derived from neural precursor cells (NPCs) in the hippocampus and SVZ of adult rats. Under the condition of treatment with 1.5-5 μM for 4 days, 40%-60% of the cells become TuJ1-positive neurons^[3].
KHS101 (0.6-5 μM; 4 d) dose-dependently inhibits BMP4-induced differentiation of adult rat hippocampal neural precursor cells (NPCs) into astrocytes and promotes their differentiation into neurons^[3].
KHS101 (0.6-5 μM; 24 h-72 h) upregulates the expression of Cdkn1 in a dose-dependent manner, and inhibits the proliferation and mitotic activity of neural precursor cells (NPCs) in the hippocampus of adult rats; after treatment with 5 μM for 72 h, the number of Ki67-positive cells decreases significantly^[3].
KHS101 (5-15 μM; 12-24 h) enhances the nuclear localization of ARNT2 in ectopically expressing 293T cells and adult rat hippocampal neural precursor cells (NPCs)^[3]. In Vivo:KHS101 (6 mg/kg; subcutaneous injection; twice daily; for 10 consecutive days) reduces the proliferation, invasion and spread of GBM tumors in intracranial patient-derived xenograft mouse models without obvious toxicity^[1].
KHS101 (6 mg/kg; subcutaneous injection; twice daily; alternating 3 or 5 days of administration per week for a total of 10 weeks) significantly improves the survival rate and reduces tumor volume in GBMX1 intracranial xenograft mouse models, with no obvious toxicity^[1].
KHS101 (6 mg/kg; subcutaneous injection; twice daily for 14 consecutive days) significantly increases the neuronal differentiation level of endogenous neural progenitor cells in adult rats, elevating the proportion of BrdU/NeuN double-positive cells from approximately 20% to approximately 40%. Meanwhile, it reduces the proliferative capacity of neural progenitor cells without inducing apoptosis or causing obvious toxicity^[3].