PX-478 2HCl
PX-478 2HCl, also called PX-478, is an experimental HIF-1α inhibitor. It inhibited HIF-1α protein at multiple levels in cancer cell lines under normoxia and hypoxia with an IC50 value of ~20-30 μM [1].
Hypoxia-inducible transcription factor HIF-1α activates target genes involved in glycolysis, erythropoiesis and angiogenesis. HIF-1α also regulates the expression of genes coding for apoptotic pathway, growth factors/receptors, cell cycle regulators, metastasis and invasiveness [1].
Under normoxic condition, the IC50 for PX-478 to inhibit HIF-1α in PC3 cells was 20-25 μmol/L, whereas the IC50 for PX-478 to inhibit HIF-1α in the DU 145 cells was ~40-50 μmol/L. in both DU 145 and PC3 cells, 1-hr hypoxia significantly upregulated HIF-1α protein. But the pretreatment with PX-478 for 20 hr under normoxia before 1-hr hypoxia attenuated the accumulation of HIF-1α induced by the 1-hr hypoxia. In PC3 cells, pretreatment with 20 μmol/L PX-478 before hypoxia inhibited HIF-1α by 40% compared to treatment with hypoxia alone. In DU 145 cells, pretreatment with 50 μmol/L PX-478 before hypoxia inhibited HIF-1α by 35% compared to treatment with hypoxia alone [1].
In nu/nu mice with C6 reporter xenografts, treatment with PX-478 at a dose of 30 mg/kg p.o. for 2 consecutive days prevented the transcriptional activity of HIF-1 in central ischemic regions of C6 tumors [2].
References:
[1]. Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells. International journal of cancer, 2008, 123(10): 2430-2437.
[2]. Schwartz DL, Powis G, Thitai-Kumar A, et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Molecular cancer therapeutics, 2009, 8(4): 947-958.
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- 2. Wenlong Zhang, Qing Zhang, et al. "Crosstalk between IL‐15Rα+ tumor‐associated macrophages and breast cancer cells reduces CD8+ T cell recruitment." Cancer Commun (Lond). 2022 Jun;42(6):536-557. PMID: 35615815
- 3. Qiu-yan Liu, Yu Zhuang, et al. "Tanshinone IIA prevents LPS-induced inflammatory responses in mice via inactivation of succinate dehydrogenase in macrophages." Acta Pharmacol Sin. 2020 Oct 7. PMID: 33028985
- 4. Peng H, Purkerson JM, et al. "Acidosis induces antimicrobial peptide expression and resistance to uropathogenic E coli infection in kidney collecting duct cells via HIF-1α." Am J Physiol Renal Physiol. 2019 Dec 16. PMID: 31841391
| Storage | Store at -20°C |
| M.Wt | 394.12 |
| Cas No. | 685898-44-6 |
| Formula | C13H20Cl4N2O3 |
| Solubility | ≥19.7 mg/mL in DMSO; ≥50 mg/mL in H2O; ≥8.42 mg/mL in EtOH |
| Chemical Name | (S)-4-(2-amino-2-carboxyethyl)-N,N-bis(2-chloroethyl)aniline oxide dihydrochloride |
| SDF | Download SDF |
| Canonical SMILES | ClCC[N+](C1=CC=C(C[C@@](N)([H])C(O)=O)C=C1)([O-])CCCl.Cl.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
DU145 cells |
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Preparation method |
The solubility of this compound in DMSO is > 19.7 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
25 μM; 18 hrs |
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Applications |
Under hypoxic condition, incubation with PX-478 for 18 hrs increased the radiosensitivity of DU145 cells, but did not significantly affect HIF-1α protein level. |
| Animal experiment [2]: | |
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Animal models |
Nu/nu mice bearing C6 reporter xenografts |
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Dosage form |
30 mg/kg; p.o.; for 2 days |
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Applications |
In nu/nu mice bearing C6 reporter xenografts, PX-478 treatment (30 mg/kg; p.o.; for 2 days) inhibited the transcriptional activity of HIF-1 in central ischemic regions of C6 tumors. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells. International journal of cancer, 2008, 123(10): 2430-2437. [2]. Schwartz DL, Powis G, Thitai-Kumar A, et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Molecular cancer therapeutics, 2009, 8(4): 947-958. |
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