2. Immunology/Inflammation NF-κB Metabolic Enzyme/Protease MAPK/ERK Pathway Cell Cycle/DNA Damage Apoptosis
  3. Reactive Oxygen Species (ROS) p38 MAPK JNK PERK Ferroptosis
  4. SB-T-101141

SB-T-101141 is a novel taxane. SB-T-101141 effectively induces a noncanonical ferroptosis to overcome Paclitaxel (HY-B0015) resistance of breast cancer. SB-T-101141 facilitates the production of iron and ferrous ions and ROS. SB-T-101141 stably binds to KHSRP to inhibit the iron-dependent expression of CISD1 related to iron homeostasis. SB-T-101141 synergistically enhances the iron-dependent activation of JNK and PERK pathways via KHSRP. SB-T-101141 suppresses breast tumor growth in MCF-7(PR)/MDA-MB-231(PR) or KHSRP knock-down MCF-7 xenograft mice model.

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SB-T-101141 Chemical Structure

SB-T-101141 Chemical Structure

CAS No. : 186348-05-0

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SB-T-101141 Related Antibodies

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Description

SB-T-101141 is a novel taxane. SB-T-101141 effectively induces a noncanonical ferroptosis to overcome Paclitaxel (HY-B0015) resistance of breast cancer. SB-T-101141 facilitates the production of iron and ferrous ions and ROS. SB-T-101141 stably binds to KHSRP to inhibit the iron-dependent expression of CISD1 related to iron homeostasis. SB-T-101141 synergistically enhances the iron-dependent activation of JNK and PERK pathways via KHSRP. SB-T-101141 suppresses breast tumor growth in MCF-7(PR)/MDA-MB-231(PR) or KHSRP knock-down MCF-7 xenograft mice model[1].

In Vitro

SB-T-101141 (1-3 μM, 12 h) efficiently induces microtubule polymerization and tubulin protein expression in MCF-7 and MDA-MB-453 cells[1].
SB-T-101141 (1-3 μM, 72 h) has potent cytotoxicity with IC50 of 0.03, 0.8 and 6.5 μM for MCF-7, MDA-MB-453 and MDA-MB-231 cells, respectively, while similar effect on normal MCF-10A cells[1].
SB-T-101141 (0.001-8 μM, 1-14 days) strongly inhibits cell proliferation and colony formation, and increased cell death in MCF-7 and MDA-MB-453 cells[1].
SB-T-101141 (9 μM, 5 days) effectively inhibits the growth of patient breast cancer organoids[1].
SB-T-101141 (1-8 μM, 12-60 h) significantly induces cell apoptosis and G2/M phase arrest at 1 μM (no efficacy at high dose), without level changes of cleavages of PARP and caspase-7 in MCF-7 and MDA-MB-453 cells[1].
SB-T-101141 (3-16 μM, 4-72 h) induces a ferroptosis-like cell death morphology with a low accumulation and increase of membrane permeability, and this effect is markedly blocked by Z-VAD-FMK and Necrostatin-1, with a mild effect on mitochondria numbers and ATP level in MCF-7 and MDA-MB-453 cells[1].
SB-T-101141 (0.17-8 μM, 0-48 h) significantly increases intracellular iron and ferrous ion as well as MDA level, and reduces GSH level without obvious effect on GPX4 expression in MCF-7, MDA-MB-453 and MCF-7PR cells[1].
SB-T-101141 (0.17-16 μM, 3-48 h) induces the total ROS (neutralized by DFOM and NAC), lipid ROS, membrane permeability the impaired cell viability and cell death, not be attenuated by DFOM, Fer-1, or Lip-1, in MCF-7, MDA-MB-453, MCF-7PR and MDA-MB-453PR cells[1].
SB-T-101141 (3-5 nM, 14 days) significantly inhibits Paclitaxel-resistant MCF-7PR and MDA-MB-231PR cells proliferation[1].
SB-T-101141 (0.25-1.5 μM, 24 h) induces Paclitaxel-resistant cell death and this effect is only only efficiently inhibited by iron chelators DFOM and CPX in MCF-7PR and MDA-MB-453PR cells[1].
SB-T-101141(0.001-3 μM, 1-14 days) is more sensitive to MCF-7 cellular with knocking down KHSRP than knocking down HDGF and CYP2S1[1].
SB-T-101141 (0.01-100 μM, 2-24 h) enhances the thermal stability of KHSRP protein without influence on KHSRP expression in MCF-7 cells[1].
SB-T-101141 (1.5-3 μM, 0-24 h) promotes lipid peroxidation and effectively reduced the mRNA and protein level of CISD1while increase of 4-HNE level via KHSRP in MCF-7 and MCF-7PR cells[1].
SB-T-101141 (10 μM, 4 h) prominently exertes ER stress-related G3BP1 granule aggregation, without affecting G3BP1 expression[1].
SB-T-101141 (0.17-16 μM, 24-48 h) increases protein level of eIF2α and induces cell death via the iron-dependent JNK and PERK signaling with in MCF-7, MDA-MB-453, MCF-7PR and MDA-MB-231PR cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

SB-T-101141 Related Antibodies

Cell Viability Assay[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 3  μM (MCF-7 cells), 8  μM (MDA-MB-453 cells)
Incubation Time: 12, 24, 36, 48, 60, 72 h
Result: Efficiently increased cell death in MCF-7 and MDA-MB-453 cells.
Induced cell death but this effect was reversed by apoptosis inhibitor (Z-VAD-FMK) (HY-16658B) and necrosis inhibitor (Necrostatin-1) (HY-15760).
Significantly increased Paclitaxel-resistant MCF-7PR and MDA-MB-231PR cells survival with IC50 of 2.7 and 0.235 μM, respectively.

Immunofluorescence[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 μM
Incubation Time: 12 h
Result: Efficiently induced microtubule polymerization.

Western Blot Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1,3 5 μM (MCF-7 cells), 8 μM (MDA-MB-453 cells)
Incubation Time: 12, 24, 36, 48, 60 h
Result: Significantly increased the tubulin protein expression in MCF-7 cells at 12 h.
Induced no cleavages of PARP and caspase-7 protein expression changes during 12-60 h in MCF-7 and MDA-MB-453 cells.

Cell Proliferation Assay[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 nM, 2  μM (MCF-7 cells), 1 nM, 5  μM (MDA-MB-453 cells)
Incubation Time: 1, 14 days
Result: Significantly decreased cell proliferation at 1 day in MCF-7 and MDA-MB-453 cells.
Strongly inhibited colony formation at 1 nM after 14 days in MCF-7 and MDA-MB-453 cells.

Apoptosis Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 μM
Incubation Time: 48 h
Result: Significantly induced cell apoptosis with late apoptosis population from 7.38% to 17.81% in MCF-7 cells and MDA-MB-453 cells (10.51% to 30.76%).

Cell Cycle Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1,3 μM (MCF-7 cells), 1,8 μM (MDA-MB-453 cells)
Incubation Time: 24 h
Result: Significantly induced G2/M phase arrest with G2/M phase population from 11.67% and 9.26% to 23.02% and 28.37% at 1 μM in MCF-7 and MDA-MB-453 cells, respectively.
Induced no G2/M phase arrest at high dose of 3 and 8 μM in MCF-7 and MDA-MB-453 cells, respectively.
In Vivo

SB-T-101141 (5  mg/kg, i.p., once every three days) strongly represses tumor growth in MCF-7(PR)/ MDA-MB-453(PR) xenografted tumor mice mode, without side effects on body weight.[1].
SB-T-101141 (5  mg/kg, i.p., once every three days) induces no inhibitory activity in tumor growth without increase of aldehyde 4-HNE level in KHSRP knock-down MCF-7 xenografted mice model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female immune-deficient BALB/c nude mice (4 weeks old) were injected subcutaneously with Estradiol cypionate (HY-B1100) following with MCF-7 cells (5 × 106 cells/mouse) or MDA-MB-453 cells (1 × 107 cells/mouse)[1].
Dosage: 5 mg/kg, Estradiol cypionate (1.5 mg/kg)
Administration: i.p., once every three days (Estradiol cypionate, once every seven days) and then measured body weight and tumor volume.
Result: Strongly repressed tumor growth in MCF-7/ MDA-MB-453 xenografted tumor mice model.
Caused no significant mouse body weight changes in MDA-MB-453 xenografted tumor mice model.
Had a strong antitumor effect on the Paclitaxel-resistant cell xenografted tumor progression without side effects on body weight.
Animal Model: Female immune-deficient BALB/c nude mice (4 weeks old) were injected subcutaneously with Estradiol cypionate following with KHSRP knock-down MCF-7 cells (6 × 106 cells/mouse)[1].
Dosage: 5 mg/kg, Estradiol cypionate (1.5 mg/kg)
Administration: i.p., once every three days (Estradiol cypionate, once every seven days) and then measured body weight and tumor volume.
Result: Induced no inhibitory activity in tumor growth without increase of lipid peroxidation product, aldehyde 4-HNE in KHSRP knock-down MCF-7 xenografted mice model
Molecular Weight

869.90

Formula

C44H55NO17
CAS No.
SMILES

CC1(C)[C@@]2(O3)[C@@H](OC3=O)[C@H](OC([C@H](O)[C@@H](NC(OC(C)(C)C)=O)/C=C(C)/C)=O)C(C)=C1[C@@H](OC(C)=O)C([C@@]4(C)[C@]([C@@](CO5)(OC(C)=O)[C@H]5C[C@@H]4O)([H])[C@@H]2OC(C6=CC=CC=C6)=O)=O
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Keywords:

SB-T-101141186348-05-0Reactive Oxygen Species (ROS)p38 MAPKJNKPERKFerroptosisc-Jun N-terminal kinaseProtein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseTaxaneAnticancerMCF-7(PR)/MDA-MB-231(PR) xenograft mice modelMCF-7PR cellsMDA-MB-231PR cellsInhibitorinhibitorinhibit

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