PM534
PM534 is a potent tubulin inhibitor (KD = 20 nM). PM534 targets and binds to the entire colchicine-binding domain (CBD) of tubulin, thereby inhibiting tubulin assembly; this leads to cell cycle arrest at the G2-M phase and induces multinucleation and apoptosis. PM534 exhibits microtubule-destabilizing agent (MDA) activity, potent broad-spectrum antitumor activity, and anti-angiogenic effects. PM534 can be used in research concerning human non-small cell lung cancer (NSCLC), breast cancer, ovarian cancer, and prostate cancer.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 2446376-25-4
- 分子式: C20H27N3O5S
- 分子量:421.51
-
保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
生物活性
製品説明
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
1.5 nM
Compound: PM534
|
Antiproliferative activity against human A549 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human A549 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
38294341 |
| HeLa | IC50 |
1.3 nM
Compound: PM534
|
Antiproliferative activity against human HeLa cells expressing tubulin betaIII assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human HeLa cells expressing tubulin betaIII assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
38294341 |
| A2780 | IC50 |
1.4 nM
Compound: PM534
|
Antiproliferative activity against human A2780 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human A2780 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
38294341 |
| HeLa | IC50 |
1.6 nM
Compound: PM534
|
Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
Antiproliferative activity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay
|
38294341 |
| BT-474 | GI50 |
2.3 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| HCC1937 | GI50 |
1.8 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| HCC1954 | GI50 |
22.4 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| MCF7 | GI50 |
2.1 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| MDA-MB-231 | GI50 |
2.2 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| MDA-MB-436 | ED50 |
2.6 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| A2780 | GI50 |
1.1 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| ES-2 | GI50 |
2.5 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| IGROV-1 | GI50 |
2.8 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| SK-OV-3 | GI50 |
2.5 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| LNCaP | GI50 |
3.0 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| PC-3 | GI50 |
1.7 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| VCaP | GI50 |
2.7 nM
|
Significantly inhibits cell activity.
Significantly inhibits cell activity.
|
41481906 |
| LoVo | GI50 |
1.9 nM
|
Overcomes drug resistance and inhibits cell growth.
Overcomes drug resistance and inhibits cell growth.
|
41481906 |
| HeLa | GI50 |
1.1 nM
|
Overcomes drug resistance and inhibits cell growth.
Overcomes drug resistance and inhibits cell growth.
|
41481906 |
体外実験
PM534 (0.06-240 nM; 72 h) inhibits the growth of tumor cells in BT-474 (GI50 = 2.3 nM), HCC1937 (GI50 = 1.8 nM), HCC1954 (GI50 = 22.4 nM), MCF7 (GI50 = 2.1 nM), MDA-MB-231 (GI50 = 2.2 nM), MDA-MB-436 (GI50 = 2.6 nM), A2780 (GI50 = 1.1 nM), ES-2 (GI50 = 2.5 nM), IGROV-1 (GI50 = 2.8 nM), SK-OV-3 (GI50 = 2.5 nM), 22Rv1 (GI50 = 2.1 nM), LN-Cap (GI50 = 3.0 nM), PC-3 (GI50 = 1.7 nM), and VCaP (GI50 = 2.7 nM) cells[2].
PM534 (10 nM; 1-24 h) exerts irreversible antiproliferative effects in MDA-MB-231 and MDA-MB-436 cells[2].
PM534 (0.5-10 nM; 24 h) inhibits cell invasion, disrupts capillary-like tubular structure formation, and destroys established networks in HUVEC cells[2].
PM534 (0.06-240 nM; 72 h) exhibits activity to overcome drug resistance and inhibit cell growth in LoVo (GI50 = 1.9 nM), LoVo-DOX (GI50 = 5.8 nM), HeLa wt (GI50 = 1.1 nM), and HeLa βIII (GI50 = 1 nM) cells[2].
PM534 (10-1000 nM; 2 h) competitively binds to the colchicine site and displaces EBI in cell lysates[2].
PM534 (0.5-10 nM; 30 min) inhibits cell adhesion activity in HUVEC cells (IC50 = 2.3 nM)[2].
PM534 (0.6-10 nM; 24 h) inhibits cell migration in HUVEC cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:A549
-
Concentration:1 nM, 2 nM
-
Incubation Time:24 h
-
Result:Induced complete disorganization of the tubulin cytoskeleton during interphase.
Abrogated the formation of the mitotic spindle.
Generated a cell phenotype of hypercondensed chromatin and aberrant chromosome distribution.
-
Cell Line:OV-3, 22Rv1, LN-Cap, PC-3, VCaP, LoVo, LoVo-DOX, HeLa, HeLa βIII
-
Concentration:Perform serial dilutions starting from 240 nM down to 0.06 nM using a 1:2.5 dilution factor
-
Incubation Time:72 h
-
Result:BT-474, HCC1937, HCC1954, MCF7, MDA-MB-231, MDA-MB-436, A2780, ES-2, IGROV-1, SK- Inhibited cell proliferation and growth in a dose-dependent manner.
-
Cell Line:MDA-MB-231, A2780, 22Rv1
-
Concentration:10 nM
-
Incubation Time:24 h
-
Result:Induced the formation of multinucleated and aberrantly divided cells.
-
Cell Line:MDA-MB-231, A2780, 22Rv1
-
Concentration:10 nM
-
Incubation Time:24 h
-
Result:Caused a pronounced accumulation of cells in the G2-M phase.
-
Cell Line:MDA-MB-231, A2780, 22Rv
-
Concentration:10 nM
-
Incubation Time:6, 15, 24, 48 h
-
Result:Upregulated the expression of cyclin B1 and phosphorylated histone H3 (pH3).
-
Cell Line:HUVEC
-
Concentration:0.6, 1.6, 4, 10 nM
-
Incubation Time:24 h
-
Result:Significantly delayed wound closure at lower concentrations and completely inhibited cell migration at concentrations above 4 nM.
-
Cell Line:HUVEC
-
Concentration:0.5, 1.0, 2.5, 5, 10 nM
-
Incubation Time:24 h
-
Result:Concentration-dependently inhibited invasion and completely abrogated cell invasion at concentrations of 5 nM and 10 nM.
体内実験
PM534 (2.5 and 5 mg/kg; intravenous injection; once weekly; for 3 consecutive weeks) exerts effects of reducing tumor volume, prolonging survival, inducing apoptosis and necrosis, and disrupting blood vessels in A2780, ES-2, MDA-MB-231, and HCC1937 xenograft mouse models[2].
PM534 (5 mg/kg; intravenous injection; single administration; for 1 week) exerts effects of overcoming multidrug resistance and significantly reducing tumor volume in LoVo, LoVo-DOX, HeLa wt, and HeLa βIII xenograft mouse models[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Athymic nu/nu mice (Female, 4-6 weeks old) were subcutaneously injected with 5 x 106 NCI-H460 cells[1]
-
Dosage:0.75, 1.1, 1.7, 2.5 mg/kg
-
Administration:i.v.; once a week; 2 weeks
-
Result:Inhibited tumor growth and improved survival rates.
-
Animal Model:Athymic nude-Foxn1nu/nu mice (Female, 4-6 weeks old) were subcutaneously injected with 5 x 106 A2780, ES-2, MDA-MB-231, HCC1937 cells[2]
-
Dosage:2.5 mg/kg (ES-2, HCC1937), 5 mg/kg (A2780, MDA-MB-231)
-
Administration:i.v.; once a week; 3 weeks
-
Result:Reduced tumor volume.
Prolonged survival.
Induced apoptosis and necrosis.
Disrupted blood vessels.
-
Animal Model:Athymic nude-Foxn1nu/nu and CB17/Icr-Prkdecid mice (male, 4-6 weeks old) were subcutaneously injected with 5 x 106 22Rv1 and VCaP cells, respectively[2]
-
Dosage:2.5 mg/kg (VCaP), 3.75 mg/kg (22Rv1)
-
Administration:i.v.; once a week; 3 weeks
-
Result:Reduce tumor volume and prolong survival.
-
Animal Model:Athymic nude-Foxn1nu/nu mice (Female, 4-6 weeks old) were subcutaneously injected with 5 x 106 LoVo, LoVo-DOX, HeLa wt, HeLa βIII cells[2]
-
Dosage:5 mg/kg
-
Administration:i.v.; single dose; 1 week
-
Result:Overcame multidrug resistance and significantly reduced tumor volume.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Apoptosis Solutions
- Protocol for Cell Cycle
- Subcutaneous Cell-Line-Derived Xenograft
- Breast Cancer Modeling
臨床実験
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
-
CAS 番号 2446376-25-4
-
分子量 421.51
-
分子式 C20H27N3O5S
-
SMILES
O=C([C@]1(N=C(SC1)/C(C)=N/O)C)N[C@@H](C2=CC(OCC3CC3)=CC(O2)=O)CCC
-
輸送条件
Room temperature in continental US; may vary elsewhere.
-
保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Lucena-Agell D,et al. PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin. J Med Chem. 2024 Feb 22;67(4):2619-2630. [Content Brief]
[2]. Aviles P, et al. PM534, a Novel Colchicine Site Tubulin Inhibitor with Broad-Spectrum and Resistance-Overcoming Antitumor Activity. Mol Cancer Ther. 2026 Jun 1;25(6):935-947. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)