5-((R)-sec-butylaMino)-N1-((1R,3r,5S)-8-(5-(cyclopropanecarbonyl)pyridin-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-MethylterephthalaMide
XL888
CAS: 1149705-71-4
Molecular Formula: C29H37N5O3
5-((R)-sec-butylaMino)-N1-((1R,3r,5S)-8-(5-(cyclopropanecarbonyl)pyridin-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-MethylterephthalaMide - Names and Identifiers
5-((R)-sec-butylaMino)-N1-((1R,3r,5S)-8-(5-(cyclopropanecarbonyl)pyridin-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-MethylterephthalaMide - Physico-chemical Properties
| Molecular Formula | C29H37N5O3 |
| Molar Mass | 503.64 |
| Density | 1.27±0.1 g/cm3(Predicted) |
| Boling Point | 695.1±55.0 °C(Predicted) |
| pKa | 14.33±0.20(Predicted) |
| Storage Condition | -20℃ |
| In vitro study | XL888 induced HER2 regression in NCI-N87 cells with an IC50 of 56 nM. XL888 inhibits NCI-N87 of HER2 overexpression, BT-474 of HER2 overexpression, MDA-MB-453 of HER2 overexpression, MET mutated MKN45, Colo-205 of B- Raf mutations, SK-MEL-28 of B- Raf mutations, EGFR-mutated HN5, EGFR-mutated NCI-H1975, and K-Ras-mutated A549 cell proliferation, IC50 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, and 4.3 nM. The effect of XL888 on Vemurafenib-sensitive and anti-Vemurafenib melanoma cell lines and melanoma cell lines with intrinsic drug resistance resulted in decreased cell growth in a dose-dependent manner with an IC50 of approximately 0.1 μm. The growth-inhibiting effect of xl888-induced G1 phase cell cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or G2-M phase cell cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell line). XL888 (300 nmol) acts on these cell lines, inducing high levels (>66%) of apoptosis and inducing mitochondrial membrane potential loss (TMRM). The cytotoxic effect of XL888 was long-lasting and cell lines cultured for 4 weeks were observed with no evidence of colony formation. Treatment of these cells with acquired resistance to BRAF inhibitors with XL888 (300 nM), treated for 48 hours, resulted in IGF1R, PDGFR β, ARAF, CRAF, and cyclin D1 degenerate, inhibiting AKT, ERK, and S6 signaling. Treatment with XL888 (300 nM) resulted in increased expression of HSP70 subtype 1, a time-dependent effect. Treatment of M229R, 1205LuR, RPMI7951, and WM39 cell lines with XL888(300 nM) for 48 hours enhanced BIM-EL, BIM-L, and BIM-S expression, and treatment of WM164R cell line induced BIM-L and BIM-S expression, treatment of the M249R cell line induced BIM-EL expression. xl888-induced HER2 regression in NCI-N87 cells with an IC50 of 56 nM. XL888 inhibits NCI-N87 of HER2 overexpression, BT-474 of HER2 overexpression, MDA-MB-453 of HER2 overexpression, MET mutated MKN45, Colo-205 of B- Raf mutations, SK-MEL-28 of B- Raf mutations, EGFR-mutated HN5, EGFR-mutated NCI-H1975, and K-Ras-mutated A549 cell proliferation, IC50 were 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, and 4.3 nM. The effect of XL888 on Vemurafenib-sensitive and anti-Vemurafenib melanoma cell lines and melanoma cell lines with intrinsic drug resistance resulted in decreased cell growth in a dose-dependent manner with an IC50 of approximately 0.1 μm. The growth-inhibiting effect of xl888-induced G1 phase cell cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or G2-M phase cell cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell line). XL888 (300 nmol) acts on these cell lines, inducing high levels (>66%) of apoptosis and inducing mitochondrial membrane potential loss (TMRM). The cytotoxic effect of XL888 was long-lasting and cell lines cultured for 4 weeks were observed with no evidence of colony formation. Treatment of these cells with acquired resistance to BRAF inhibitors with XL888 (300 nM), treated for 48 hours, resulted in degradation of IGF1R, PDGFR β, ARAF, CRAF, and cyclin D1, inhibition of AKT, ERK, and S6 signal. Treatment with XL888 (300 nM) resulted in increased expression of HSP70 subtype 1, a time-dependent effect. XL888(300 nM) treatment M229R, 1205LuR, RPMI7951, And WM39 cell line for 48 hours, enhanced BIM-EL, BIM-L, and BIM-S expression, treated WM164R cell line, induced BIM-L and BIM-S expression, treated M249R cell line, induced BIM-EL expression. |
| In vivo study | Treatment of SCID mice bearing M229R and 1205LuR xenografts with XL888 (100 mg/kg) significantly induced regression and growth inhibition (50%). Treatment with XL888 for 15 days significantly enhanced intratumoral HSP70 expression (8.6-fold) compared to the control group. Treatment of M229R xenografts with XL888 promoted apoptosis in vivo, leading to increased TUNEL staining, which correlated with increased BIM expression and decreased Mcl-1 expression. Treatment of SCID mice bearing both M229R and 1205LuR xenografts with XL888 (100 mg/kg) significantly induced regression and growth inhibition (50%). Treatment with XL888 for 15 days significantly enhanced intratumoral HSP70 expression (8.6-fold) compared to the control group. Treatment of M229R xenografts with XL888 promoted apoptosis in vivo, leading to increased TUNEL staining, which correlated with increased BIM expression and decreased Mcl-1 expression. |
5-((R)-sec-butylaMino)-N1-((1R,3r,5S)-8-(5-(cyclopropanecarbonyl)pyridin-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-MethylterephthalaMide - Reference Information
| biological activity | XL888 is an ATP competitive HSP90 inhibitor with IC50 of 24 nM. Phase 1 XL888 An ATP-competitive HSP90 inhibitor with an IC50 of 24 nM. Phase 1 |
| in vitro study | XL888 acts on NCI-N87 cells to induce HER2 degeneration with IC50 of 56 nM. XL888 inhibits HER2 overexpressing NCI-N87, HER2 overexpressing BT-474, HER2 overexpressing MDA-MB-453, MET mutant MKN45, B- Raf mutant Colo-205, B- Raf mutant SK-MEL-28, EGFR mutant HN5, EGFR mutant NCI-H1975, and K-Ras mutant A549 cell proliferation, IC50 is 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, and 4.3 nM, respectively. XL888 acts on Vemurafenib-sensitive and anti-Vemurafenib melanoma cell lines and melanoma cell lines with intrinsic drug resistance, resulting in reduced cell growth. This effect is dose-dependent, with an IC50 of about 0.1 μM. The effect of XL888 on growth inhibition is related to the induction of G1 phase cell cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or G2-M phase cell cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell lines). XL888 (300 nmol) acts on these cell lines to induce high levels (>66%) of apoptosis and mitochondrial membrane potential loss (TMRM). The cytotoxic effect of XL888 was persistent, and cell lines cultured for 4 weeks were observed, and there was no sign of colony formation. XL888 treatment (300 nM) treated these cells with acquired BRAF inhibitor resistance for 48 hours, resulting in degradation of IGF1R, PDGFRβ, ARAF, CRAF, and cyclin D1, inhibiting AKT, ERK, and S6 signals. XL888 (300 nM) treatment resulted in increased expression of HSP70 subtype 1, which was time-dependent. XL888(300 nM) treated M229R, 1205LuR, RPMI7951, and WM39 cell lines for 48 hours, enhanced BIM-EL, BIM-L, and BIM-S expression, treated WM164R cell line, induced BIM-L and BIM-S expression, treated M249R cell line, induced BIM-EL expression. XL888 acts on NCI-N87 cells to induce HER2 degeneration with IC50 of 56 nM. XL888 inhibits HER2 overexpressing NCI-N87, HER2 overexpressing BT-474, HER2 overexpressing MDA-MB-453, MET mutant MKN45, B- Raf mutant Colo-205, B- Raf mutant SK-MEL-28, EGFR mutant HN5, EGFR mutant NCI-H1975, and K-Ras mutant A549 cell proliferation, IC50 is 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, and 4.3 nM, respectively. XL888 acts on Vemurafenib-sensitive and anti-Vemurafenib melanoma cell lines and melanoma cell lines with intrinsic drug resistance, resulting in reduced cell growth. This effect is dose-dependent, with an IC50 of about 0.1 μM. The effect of XL888 on growth inhibition is related to the induction of G1 phase cell cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or G2-M phase cell cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell lines). XL888 (300 nmol) acts on these cell lines to induce high levels (>66%) of apoptosis and mitochondrial membrane potential loss (TMRM). The cytotoxic effect of XL888 was persistent, and cell lines cultured for 4 weeks were observed without evidence of colony formation. XL888 treatment (300 nM) treated these cells with acquired BRAF inhibitor resistance for 48 hours, resulting in degradation of IGF1R, PDGFRβ, ARAF, CRAF, and cyclin D1, inhibiting AKT, ERK, and S6 signals. XL888 (300 nM) treatment resulted in increased expression of HSP70 subtype 1, which was time-dependent. XL888(300 nM) treated M229R, 1205LuR, RPMI7951, and WM39 cell lines for 48 hours, enhanced BIM-EL, BIM-L, and BIM-S expression, treated WM164R cell line, induced BIM-L and BIM-S expression, treated M249R cell line, induced BIM-EL expression. |
| in vivo study | XL888 (100 mg/kg) treated SCID mice carrying M229R and 1205LuR transplanted tumors, significantly induced recession and growth inhibition (50%). Compared with the control group, the expression of HSP70 in tumor was significantly enhanced by XL888 treatment for 15 days (8.6 times). XL888 treatment of M229R transplanted tumor promotes apoptosis in vivo, resulting in increased TUNEL staining, which is related to increased BIM expression and decreased Mcl-1 expression. XL888 (100 mg/kg) treated SCID mice carrying M229R and 1205LuR transplanted tumors, which significantly induced recession and growth inhibition (50%). Compared with the control group, the expression of HSP70 in tumor was significantly enhanced by XL888 treatment for 15 days (8.6 times). XL888 treatment of M229R transplanted tumor promotes apoptosis in vivo, resulting in increased TUNEL staining, which is related to increased BIM expression and decreased Mcl-1 expression. |
| target | TargetValue HSP90 (Cell-free say) 24 nM |
| Target | Value |
| HSP90 (Cell-free assay) | 24 nM |
Last Update：2024-04-09 21:50:46
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Product Name: XL888 Visit Supplier Webpage Request for quotation
CAS: 1149705-71-4
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Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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CAS: 1149705-71-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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