HS-72

HS-72 is a selective allosteric inducible heat shock protein 70 Hsp70i inhibitor. HS-72 reduces ATP affinity of Hsp70i, elevates caspase 3/7 apoptotic activity, and promotes degradation of Hsp70 client proteins, including HER2 and Akt, and blocks DENV entry by disrupting Hsp70i association with the DENV receptor complex. HS-72 can be used for breast cancer and dengue virus infection research^[1][2]. In Vitro:HS-72 acts as an allosteric inhibitor of Hsp70i. It only reduces the ATP-binding affinity of Hsp70i without inhibiting its intrinsic ATPase activity, and can induce conformational rearrangement of purified Hsp70 protein^[1].
HS-72 (0.001-0.1 mM) was identified via FLECS chemoproteomic screening. Biochemical tests including affinity pull-down, thermofluor melting assay and limited proteolysis-mass spectrometry verify that HS-72 selectively binds Hsp70i over constitutive Hsc70, while Hsp90 recovery is considered nonspecific in the affinity-resin assay^[1].
HS-72 (25, 50 μM; 48-72 h) inhibits proliferation of BT474, MCF-7 and SkBr3 breast cancer cells, while non-tumorigenic MCF10A and RWPE1 cells are relatively insensitive to HS-72^[1].
HS-72 (1-100 μM; 24 h) dose-dependently elevates caspase 3/7 apoptotic activity in BT474, HeLa, HepG2, T47D and LNCaP tumor cell lines^[1].
HS-72 (10, 50 μM; 24 h) promotes degradation of Hsp70 client proteins HER2 and Akt in BT474 and MCF-7 breast cancer cells, and shows stronger degradation activity when combined with HS-10^[1].
HS-72 (50, 100 μM; 18 h) induces accumulation of insoluble mutant HttQ74-GFP aggregates in PC12 neuronal cells^[1].
HS-72 (50-100 nmol/mL; 1 h pretreatment; 24 h post-infection) dose-dependently reduces DENV infection in U937+DC-SIGN cells while maintaining cell viability at concentrations below 90 nmol/mL^[2].
HS-72 reduces infectious DENV production in a foci forming assay, with an EC₅₀ of 22.8 nmol/mL^[2].
HS-72 (75 nmol/mL) inhibits DENV infection at the early stage of the viral life cycle, and significantly reduces viral RNA at the entry stage in U937+DC-SIGN cells^[2].
HS-72 (75 nmol/mL; 1 h pretreatment) disrupts the in situ interactions of Hsp70i with DENV E protein and DC-SIGN at 4 h post-infection, indicating inhibition of Hsp70i association with the DENV receptor complex^[2].
In Vivo:HS-72 (1-30 mg/kg; i.p.; twice a week; for 60 days) causes no obvious body weight loss or lethal toxicity in wild-type FVB female mice^[1].
HS-72 (20 mg/kg; i.p.; twice a week; for 2 days of administration, blood sampling on day 5) induces no abnormal hematological, hepatic and renal biochemical parameters in wild-type FVB female mice ^[1].
HS-72 (20 mg/kg; i.p.; twice a week; for 21 days) inhibits tumor growth in a HER2-overexpressing MMTV-neu spontaneous breast tumor mouse model^[1].
HS-72 (20 mg/kg; i.p.; twice a week or once daily) prolongs median survival in a HER2-overexpressing MMTV-neu spontaneous breast tumor mouse model; twice-weekly dosing prolongs median survival by 6 days, and once-daily dosing prolongs median survival by 13 days^[1].