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.
For research use only. We do not sell to patients.
- CAS No.: 1118861-60-1
- Formula: C20H24N6O
- Molecular Weight:364.44
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
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Hsp70i |
Caspase 3 |
Caspase 7 |
Akt |
HER2 |
DENV |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:BT474, MCF-7, SkBr3
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Concentration:25, 50 μM
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Incubation Time:48, 72 h
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Result:Inhibited proliferation of BT474, MCF-7 and SkBr3 breast cancer cells.
Non-tumorigenic MCF10A and RWPE1 cells were relatively insensitive under the same experimental context.
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Cell Line:BT474, HeLa, HepG2, T47D, LNCaP
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Concentration:1, 10, 25, 50, 100 μM
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Incubation Time:24 h
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Result:Elevated caspase 3/7 activity in a dose-dependent manner in all tested tumor cell lines.
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Cell Line:BT474, MCF-7
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Concentration:10, 50 μM
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Incubation Time:24 h
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Result:Single drug treatment promoted the degradation of Hsp70 client proteins HER2 and Akt in BT474 and MCF-7 cells.
Combined HS-10 drug administration exerted stronger degradation effects on HER2 and Akt than single-drug monotherapy.
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Cell Line:U937+DC-SIGN
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Concentration:50, 70, 80, 90, 100 nmol/mL
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Incubation Time:1 h pretreatment; 24 h post-infection
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Result:Reduced the percentage of DENV-infected cells in a dose-dependent manner.
DENV infection resulted in 56% infected cells in the control group, while HS-72 reduced infection to 34%, 15%, 9%, 6% and 4% at 50, 70, 80, 90 and 100 nmol/mL, respectively.
Cell viability was maintained at concentrations below 90 nmol/mL.
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Cell Line:U937+DC-SIGN
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Concentration:75 nmol/mL
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Incubation Time:1 h pretreatment; 1 h attachment at 4°C; 1 h entry at 37°C
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Result:Inhibited DENV infection at the entry stage.
Significantly reduced viral RNA during the entry stage according to qPCR analysis, while the time-of-addition assay showed that HS-72 was effective when added before infection, at infection, or 1 h post-infection.
Parmacokinetics
| Species | Dose | Route | T1/2 |
|---|---|---|---|
| Mice[1] | 20 mg/kg | i.p. | 0.4 h |
In Vivo
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wild-type FVB female mice[1]
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Dosage:1, 5, 10, 20, 30 mg/kg
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Administration:Intraperitoneal injection (i.p.); twice a week; for 60 days
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Result:No obvious body weight loss or lethal toxicity was observed across all tested dosage groups during the whole administration cycle.
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Animal Model:Wild-type FVB female mice[1]
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Dosage:20 mg/kg
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Administration:Intraperitoneal injection (i.p.); injected on day 1 and day 4; blood samples collected on day 5
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Result:Complete blood count, liver and renal function indicators showed no significant differences from untreated control mice.
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Animal Model:HER2-overexpressing MMTV-neu spontaneous breast tumor mouse model[1]
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Dosage:20 mg/kg
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Administration:Intraperitoneal injection (i.p.); twice weekly; for 21 days
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Result:Was well tolerated in vivo.
Inhibited tumor growth in the HER2-overexpressing MMTV-neu spontaneous breast tumor model after twice-weekly administration for 21 days.
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Animal Model:HER2-overexpressing MMTV-neu spontaneous breast tumor mouse model survival assay[1]
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Dosage:20 mg/kg
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Administration:Intraperitoneal injection (i.p.); twice a week or once daily
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Result:Prolonged median survival compared with untreated animals.
Twice-weekly dosing prolonged median survival by 6 days.
Once-daily dosing prolonged median survival by 13 days.
Chemical Information
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CAS No. 1118861-60-1
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Molecular Weight 364.44
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Formula C20H24N6O
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SMILES
O=C(NC1=NC2=CC=CC=C2N1CCC)C3CN(CCC3)C4=NC=CN=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Research Protocol for Infectious Diseases
Infectious-disease experiments test how pathogens interact with host barriers, innate immune receptors, inflammatory signaling, pathogen replication, and tissue injury; pattern-recognition receptors such as TLRs, RIG-I-like receptors, NOD-like receptors, and inflammasomes detect microbial molecules and activate NF-κB, interferon, and cytokine responses. The central hypothesis is that infection severity reflects the balance between pathogen burden and host response: protective inflammation restricts pathogen growth, whereas excessive or mislocalized inflammation contributes to tissue damage and disease phenotype. Unresolved questions include which host pathways are protective versus pathogenic, why some infection models fail to translate to human disease, and which combined readouts best predict clinically relevant infection outcomes.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
[1]. Howe MK et al. Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70. Chem Biol. 2014 Dec 18;21(12):1648-59. [Content Brief]
[2]. Howe MK, Speer BL, Hughes PF, Loiselle DR, Vasudevan S, Haystead TAJ. An inducible heat shock protein 70 small molecule inhibitor demonstrates anti-dengue virus activity, validating Hsp70 as a host antiviral target. Antiviral Res. 2016;130:81-92. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HS-72 Related Classifications
HY-117252 Related Classifications
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Keywords
- HS-72
- 1118861-60-1
- HS72
- HS 72
- HSP
- EGFR
- Akt
- Dengue Virus
- Caspase
- Hsp70 inhibitor
- Hsp70i
- Hsp72
- HSPA1A
- HSPA1B
- Hsc70 selectivity
- allosteric inhibitor
- ATP affinity
- HER2
- protein degradation
- BT474
- MCF-7
- SkBr3
- MCF10A
- RWPE1
- MMTV-neu breast tumor model
- HER2-positive breast cancer
- Dengue virus
- DENV
- anti-DENV activity
- antiviral activity
- Hsp70i host factor
- U937+DC-SIGN
- Huh7
- Vero
- DENV E protein
- DC-SIGN
- DENV receptor complex
- viral entry
- viral RNA
- foci forming assay
- proximity ligation assay
- monocytes
- liver cells
- dengue virus infection
- Inhibitor
- inhibitor
- inhibit