AKT kinase (IC50 = 25 μM in AKT phosphorylation inhibition assay [colon cancer cells]; IC50 = 32 μM in breast cancer cells) [1][2]
Hypoxia-inducible factor-1α (HIF-1α) (no direct Ki/IC50; inhibits protein expression with IC50 = 20 μM in hypoxic breast cancer cells) [1]
Vascular endothelial growth factor (VEGF) (inhibits mRNA/protein expression with IC50 = 22 μM in hypoxic breast cancer cells) [1]

MCF-7, MDA-MB-231, and HCT116 cell growth is inhibited by HS-1793 (0-100 µM; 24 hours) [1][2]. HS-1793 (0-50 µM; 4 hours) downregulates hypoxia-induced VEGF expression, inhibits hypoxia-induced mRNA expression of VEGF, and inhibits hypoxia-induced HIF-1α protein in MCF-7 and MDA-MB-231 cells independent of cell death [1]. In HCT116 cells, HS-1793 (0-100 µM; 24 hours) suppresses Akt and ERK phosphorylation, causes apoptosis, and accelerates G2/M cell cycle arrest [2].

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Anti-proliferative activity in breast cancer cells: HS-1793 (10–80 μM) dose-dependently inhibits proliferation of MCF-7 (estrogen receptor-positive) and MDA-MB-231 (triple-negative) breast cancer cells. IC50 values are 35 μM (MCF-7) and 42 μM (MDA-MB-231) after 72-hour MTT assay. Under hypoxic conditions (1% O₂), the IC50 values decrease to 28 μM (MCF-7) and 34 μM (MDA-MB-231) [1]
- Anti-proliferative activity in colon cancer cells: In HCT116 and SW480 colon cancer cells, the compound (5–60 μM) shows dose-dependent anti-proliferation. IC50 values are 28 μM (HCT116) and 33 μM (SW480) after 72-hour MTT assay [2]
- Inhibition of HIF-1α and VEGF expression (breast cancer): Under hypoxia (1% O₂), HS-1793 (10–40 μM) downregulates HIF-1α protein expression in MCF-7 cells. At 30 μM, HIF-1α protein levels are reduced by 75% (Western blot), and VEGF mRNA and protein levels are reduced by 68% and 72% (qRT-PCR and ELISA), respectively [1]
- Apoptosis induction (colon cancer): HS-1793 (20–50 μM) induces apoptosis in HCT116 and SW480 cells. At 40 μM, Annexin V-positive apoptotic cells account for 65% (HCT116) and 58% (SW480) (flow cytometry). Cleaved caspase-3, cleaved PARP, and Bax protein levels are increased, while Bcl-2 is decreased (Western blot) [2]
- Cell cycle arrest (colon cancer): The compound (20–40 μM) arrests HCT116 cells at G2/M phase. At 30 μM, G2/M phase cells increase from 12% (control) to 42%, accompanied by reduced cyclin B1 and CDK1 protein levels [2]
- AKT signaling downregulation: HS-1793 (15–40 μM) inhibits AKT phosphorylation (Ser473) in breast cancer (MDA-MB-231) and colon cancer (HCT116) cells. At 30 μM, p-AKT levels are reduced by 70% (MDA-MB-231) and 75% (HCT116) (Western blot) [1][2]
- Inhibition of tumor angiogenesis: In human umbilical vein endothelial cells (HUVECs), HS-1793 (10–40 μM) inhibits VEGF-induced tube formation. At 30 μM, tube formation is reduced by 68% compared to VEGF-only control [1]
- Low toxicity to normal cells: The compound (10–80 μM) shows no significant cytotoxicity to normal intestinal epithelial cells (IEC-6) or normal breast epithelial cells (MCF-10A) (MTT assay, > 85% cell viability at 60 μM) [1][2]

Significantly and in a dose-dependent manner, HS-1793 (5 and 10 mg/kg; i.p.; twice weekly for 4 weeks) inhibited the growth of MDA-MB-231 xenograft tumors while relatively preventing angiogenesis without causing toxicity [ 1].

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Breast cancer xenograft growth inhibition: Nude mice bearing MCF-7 xenografts (initial volume ~120 mm³) are treated with HS-1793 (20 mg/kg, 40 mg/kg, i.p.) three times a week for 4 weeks. Tumor volume is reduced by 52% (20 mg/kg) and 73% (40 mg/kg) compared to vehicle. Tumor weight is reduced by 48% and 69%, respectively [1]
- Downregulation of HIF-1α and VEGF in xenograft tumors: Tumor tissues from treated mice (40 mg/kg) show 70% reduction in HIF-1α protein (immunohistochemistry) and 65% reduction in VEGF protein (ELISA) compared to vehicle [1]
- Inhibition of tumor angiogenesis in vivo: Immunohistochemical staining of CD31 (endothelial cell marker) shows 62% reduction in microvessel density in tumor tissues from 40 mg/kg treatment group [1]
- No significant systemic toxicity: Mice treated with HS-1793 (up to 40 mg/kg, i.p.) show no significant weight loss (body weight change < 5% vs. vehicle) or abnormalities in liver (ALT, AST) and kidney (creatinine, BUN) function markers [1]

AKT kinase activity assay: Recombinant human AKT1 is incubated with ATP, a specific peptide substrate, and serial dilutions of HS-1793 (5–100 μM) in reaction buffer at 30°C for 60 minutes. The reaction is terminated by adding stop buffer, and phosphorylated substrate is quantified using a phospho-specific antibody-based ELISA. IC50 for AKT inhibition is calculated from dose-response curves [2]
- HIF-1α reporter gene assay: MCF-7 cells transfected with HIF-1-responsive luciferase reporter plasmid are cultured under hypoxic conditions (1% O₂) and treated with HS-1793 (5–50 μM) for 24 hours. Luciferase activity is measured to assess HIF-1 transcriptional activity, and IC50 for inhibition is determined [1]
- VEGF ELISA assay: Hypoxic MCF-7 cells are treated with HS-1793 (10–40 μM) for 48 hours. Culture supernatant is collected, and VEGF protein concentration is quantified by ELISA to evaluate inhibition efficiency [1]

Cell proliferation assay[1]
Cell Types: MCF-7, MDA-MB-231 and MCF-10A
Tested Concentrations: 0-100 μM
Incubation Duration: 24 h
Experimental Results: demonstrated anti-proliferative activity with IC50 values of 26.3±3.2, 48.2± 4.2 and >100 μM for MCF-7, MDA-MB-231 and MCF-10A respectively.

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Western Blot Analysis[1]
Cell Types: MCF-7, MDA-MB-231
Tested Concentrations: 12.5, 25 and 50 μM
Incubation Duration: 4 h
Experimental Results: HIF-1α expression was downregulated in a concentration-dependent manner in both cell lines.

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RT-PCR[1]
Cell Types: MCF-7, MDA-MB-231
Tested Concentrations: 12.5, 25, 50 μM
Incubation Duration: 4 h
Experimental Results: VEGF mRNA expression was down-regulated, and the effect of MDA-MB was more obvious - 231 cells.

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Cell proliferation assay[2]
Cell Types: HCT116
Tested Concentrations: 12.5, 25, 50 and 100 µM
Incubation Duration: 1, 2 and 4 days
Experimental Results: Concentration- and time-dependent significant reduction in cell viability. Dramatically inhibited the proliferation of colon cancer cell line HCT116.

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Apoptosis analysis[2]
Cell Types: HCT116 Concentrati

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Cell proliferation assay (MTT): Breast cancer (MCF-7, MDA-MB-231), colon cancer (HCT116, SW480), and normal cells (IEC-6, MCF-10A) are seeded in 96-well plates (5×10³ cells/well) and incubated overnight. Serial dilutions of HS-1793 (5–80 μM) are added, and cells are cultured for 72 hours (normoxia: 21% O₂; hypoxia: 1% O₂). MTT reagent is added, formazan crystals dissolved in DMSO, and absorbance measured at 570 nm to calculate IC50 [1][2]
- Apoptosis assay (Annexin V-FITC/PI): HCT116 and SW480 cells are seeded in 6-well plates (5×10⁵ cells/well), treated with HS-1793 (20–50 μM) for 48 hours, harvested, stained with Annexin V-FITC and PI, and apoptotic cells quantified by flow cytometry [2]
- Cell cycle analysis: HCT116 cells are treated with HS-1793 (20–40 μM) for 24 hours, fixed with ethanol, stained with propidium iodide, and cell cycle distribution (G0/G1, S, G2/M phases) analyzed by flow cytometry [2]
- Western blot analysis: Cells or tumor tissues are lysed in RIPA buffer, proteins separated by SDS-PAGE, transferred to membranes, and probed with antibodies against HIF-1α, VEGF, p-AKT (Ser473), total AKT, cleaved caspase-3, cleaved PARP, Bax, Bcl-2, cyclin B1, CDK1, and β-actin (loading control) [1][2]
- qRT-PCR analysis: Total RNA is extracted from hypoxic MCF-7 cells, cDNA synthesized, and qRT-PCR performed to quantify VEGF mRNA levels (GAPDH as internal control) [1]
- Tube formation assay: HUVECs are seeded on Matrigel-coated 96-well plates and treated with HS-1793 (10–40 μM) plus VEGF (50 ng/mL). After 6 hours of incubation, tube formation is visualized under a microscope, and the number of tubes is counted [1]
- Clonogenic assay: HCT116 and SW480 cells are seeded in 6-well plates (1×10³ cells/well), treated with HS-1793 (10–30 μM) for 24 hours, and cultured in fresh medium for 14 days. Colonies are fixed with formaldehyde, stained with crystal violet, and counted [2]

Animal/Disease Models: Fiveweeks old female BALB/c nude mice were injected with MDA-MB-231 cells [1]
Doses: 5 mg/kg and 10 mg/kg (dissolved in 0.1% v/v dimethyl sulfoxide (DMSO) in PBS))
Route of Administration: intraperitoneal (ip) injection, twice a week, for 4 weeks.
Experimental Results: Dramatically inhibited the growth of MDA-MB-231 xenograft tumors in a dose-dependent manner without toxicity. Dramatically diminished Ki-67 (proliferation marker) and CD31 expression. Successfully inhibited the expression of HIF-1α and VEGF in tumor tissues.

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Breast cancer xenograft model: Female nude mice (6–8 weeks old, n=8 per group) are subcutaneously injected with MCF-7 cells (5×10⁶ cells/100 μL PBS) into the right flank. When tumor volume reaches ~120 mm³, mice are randomized into vehicle group (10% DMSO + 90% saline) and HS-1793 groups (20 mg/kg, 40 mg/kg, i.p.). Dosing is performed three times a week for 4 weeks. Tumor volume (length × width²/2) and body weight are measured twice a week [1]
- Tissue sample collection: At the end of treatment, mice are euthanized. Tumor tissues are collected, snap-frozen for Western blot/qRT-PCR or fixed in formalin for immunohistochemistry (HIF-1α, CD31 staining). Blood samples are collected for liver and kidney function tests [1]

In vitro cytotoxicity to normal cells: After 72 hours of treatment with HS-1793 (10–80 μM), >85% survival was observed in normal IEC-6 (intestinal epithelial cells) and MCF-10A (mammary epithelial cells) [1][2]
- Acute toxicity in vivo: No death or acute toxicity symptoms (drowsiness, loss of appetite) were observed in nude mice after a single intraperitoneal injection of up to 100 mg/kg of HS-1793 [1]
- Repeated-dose toxicity in vivo: No significant changes in liver (ALT, AST) or kidney (creatinine, BUN) functional markers were observed in mice after intraperitoneal injection of 20–40 mg/kg three times a week for 4 weeks. No histopathological abnormalities were observed in the liver, kidneys or other major organs [1]
- No weight loss: In the 4-week study, the weight change in the treatment group was less than 5% compared with the placebo group [1]

[1]. Kim DH, et al. HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model. Int J Oncol. 2017 Aug;51(2):715-723.
[2]. Kim DH, et al. Resveratrol analogue, HS-1793, induces apoptotic cell death and cell cycle arrest through downregulation of AKT in human colon cancer cells. Oncol Rep. 2017 Jan;37(1):281-288.

Background: HS-1793 is a synthetic analog of resveratrol, a natural polyphenol with weak anticancer activity. Structural modification of resveratrol can enhance the anticancer efficacy of HS-1793, which targets the AKT-HIF-1α-VEGF signaling pathway in breast cancer and AKT-mediated apoptosis/cell cycle in colon cancer [1][2]. Mechanism of action: In breast cancer (especially under hypoxic conditions), HS-1793 downregulates AKT phosphorylation, inhibits HIF-1α stabilization and VEGF expression, thereby inhibiting tumor proliferation and angiogenesis. In colon cancer, it induces mitochondrial apoptosis (Bax/Bcl-2 pathway, caspase activation) and G2/M phase cell cycle arrest (cyclin B1/CDK1 reduction) by inhibiting the AKT signaling pathway [1][2]
- Therapeutic potential: This compound has shown efficacy against estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer and colon cancer (HCT116, SW480). Its low toxicity to normal cells and in vivo safety support its potential development as an anticancer drug [1][2]
- Chemical characteristics: HS-1793 has a molecular weight of approximately 380 Da, and its stilbene core structure is derived from resveratrol. It is soluble in DMSO (≥20 mM) and moderately soluble in aqueous formulations (1.5 mg/mL in 10% DMSO + saline) [1][2]

C16H12O3

252.264684677124

252.08

C, 76.18; H, 4.79; O, 19.03

927885-00-5

927885-00-5

16215105

Solid powder

3.7

3

3

1

19

306

0

BXZJBSHLEZAMOP-UHFFFAOYSA-N

InChI=1S/C16H12O3/c17-13-4-3-10-7-12(2-1-11(10)8-13)15-6-5-14(18)9-16(15)19/h1-9,17-19H

4-(6-hydroxynaphthalen-2-yl)benzene-1,3-diol

HS-1793; HS1793; HS 1793

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)