| Identification | Back Directory | [Name]
Benzenesulfonamide, 4-(1-azetidinyl)-N-(9,10-dihydro-3,4-dihydroxy-9,10-dioxo-2-anthracenyl)- | [CAS]
2414908-90-8 | [Synonyms]
HKB99
Benzenesulfonamide, 4-(1-azetidinyl)-N-(9,10-dihydro-3,4-dihydroxy-9,10-dioxo-2-anthracenyl)- | [Molecular Formula]
C23H18N2O6S | [MOL File]
2414908-90-8.mol | [Molecular Weight]
450.46 |
| Chemical Properties | Back Directory | [Boiling point ]
679.8±65.0 °C(Predicted) | [density ]
1.598±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
6.25±0.20(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
HKB99 is an allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1). HKB99 induces apoptosis. HKB99 inhibits the formation of invasive pseudopodia and inhibits migration. HKB99 increases the oxidative stress, activates JNK/c-Jun and suppresses AKT and ERK. HKB99 can be used for the research of non-small-cell lung cancer (NSCLC)[1][2]. | [in vivo]
HKB99 (35-100 mg/kg; i.p.; daily or once every 3 days) significantly suppresses tumor growth and augments the tumoricidal effect of Erlotinib in mouse xenografts. HKB99 restrains the tumor metastasis after intravenous NSCLC cell injection[2].
| Animal Model: | Female BALB/c nu/nu mice (4 weeks) (NSCLC cells were injected subcutaneously on two sites per mouse) or (HCC827-Luc and HCC827ER9-Luc cells about 5 x 106 were injected through the tail vein injection)[2] | | Dosage: | 35, 100 mg/kg | | Administration: | Intraperitoneal injection (i.p.); daily or once every 3 days | | Result: | Attenuated tumor growth of PC9 xenografts in a murine subcutaneous model.
The T/C ratio was 32.97%, while tumors in combination with Erlotinib were almost completely abrogated (T/C ratio of 9.46%) in PC9 xenografts.
Induced much tumor necrosis in the PC9 xenografts.
Tumor weight was relevantly regressed in PC9 xenografts.
Combination with Erlotinib caused complete ablation of the tumors in HCC827 xenografts.
Significantly inhibited the HCC827ER9 xenografts’ growth with a T/C ratio of 34.76%.
Ablated the massive colonization and metastasis foci of HCC827-Luc and HCC827ER9-Luc, while the control group showed areas of high fluorescence, representing tumor foci, mainly in the lungs and abdominal organs.
The average bioluminescence intensity did not increase.
No death or weight loss over 10% was documented, indicating no subacute toxicity.
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| [References]
[1] Liang Q, et al. HKB99, an allosteric inhibitor of phosphoglycerate mutase 1, suppresses invasive pseudopodia formation and upregulates plasminogen activator inhibitor-2 in erlotinib-resistant non-small cell lung cancer cells. Acta Pharmacol Sin. 2021 Jan;42(1):115-119. DOI:10.1038/s41401-020-0399-1
[2] Huang K, et al. A Novel Allosteric Inhibitor of Phosphoglycerate Mutase 1 Suppresses Growth and Metastasis of Non-Small-Cell Lung Cancer. Cell Metab. 2019 Dec 3;30(6):1107-1119.e8. DOI:10.1016/j.cmet.2019.09.014 |
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| Company Name: |
Biorbyt Ltd.
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| Tel: |
+44 (0)1223 859 353 |
| Website: |
http://www.biorbyt.com |
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