Rimiducid

编号: 25100

Cas号: 195514-63-7

纯度: 98% Min.

Rimiducid, also known as AP1903, is a lipid-permeable bivalent "dimerizer" drug that binds FKBP and induces Fas cross-linking. AP1903 induced iCasp9 activation, which led to the apoptosis of specific undifferentiated PSCs in vitro and in vivo. AP1903 elicites potent and dose-dependent apoptosis of cells in culture expressing dimerizer-dependent Fas constructs, with an EC50 of ≈0.1 nM. Intravenous administration of AP1903 produces cross-linking of the drug-binding domains of this chimeric protein, which in turn dimerizes caspase9 and activates the downstream executioner caspase 3 molecule, resulting in cellular apoptosis. NOTE: Rimiducid (AP1903) exists as a single diastereomer and a mixture of rotamer as seen in NMR and HPLC analytical reports.

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化学信息

名称	Rimiducid
Iupac 化学名称	2-Piperidinecarboxylic acid, 1-[(2S)-1-oxo-2-(3,4,5-trimethoxyphenyl)butyl]-, 2,2′-[1,2-ethanediylbis[imino(2-oxo-2,1-ethanediyl)oxy-3,1-phenylene[(1R)-3-(3,4-dimethoxyphenyl)propylidene]]] ester, (2S,2′S)-
同义词	AP1903; AP 1903; AP-1903; Rimiducid;
英文同义词	AP1903; AP 1903; AP-1903; Rimiducid;
分子式	C78H98N4O20
分子量	1411.63
Smile	COC1=CC=C(CC[C@@H](OC([C@H]2N(C([C@H](C3=CC(OC)=C(OC)C(OC)=C3)CC)=O)CCCC2)=O)C4=CC=CC(OCC(NCCNC(COC5=CC([C@H](OC([C@H]6N(C([C@H](C7=CC(OC)=C(OC)C(OC)=C7)CC)=O)CCCC6)=O)CCC8=CC=C(OC)C(OC)=C8)=CC=C5)=O)=O)=C4)C=C1OC
InChiKey	GQLCLPLEEOUJQC-ZTQDTCGGSA-N
InChi	InChI=1S/C78H98N4O20/c1-13-57(53-43-67(93-7)73(97-11)68(44-53)94-8)75(85)81-37-17-15-25-59(81)77(87)101-61(31-27-49-29-33-63(89-3)65(39-49)91-5)51-21-19-23-55(41-51)99-47-71(83)79-35-36-80-72(84)48-100-56-24-20-22-52(42-56)62(32-28-50-30-34-64(90-4)66(40-50)92-6)102-78(88)60-26-16-18-38-82(60)76(86)58(14-2)54-45-69(95-9)74(98-12)70(46-54)96-10/h19-24,29-30,33-34,39-46,57-62H,13-18,25-28,31-32,35-38,47-48H2,1-12H3,(H,79,83)(H,80,84)/t57-,58-,59-,60-,61+,62+/m0/s1
Cas号	195514-63-7
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包装	价格	库存	纯度	备货期
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外观性状	类白色固体
纯度	98% Min.
存储	0-4℃，可保存几天到几周；-20℃，可保存几个月。
可溶性	溶于DMSO等有机溶剂
处理方式
运输条件	可以在室温下进行运输。
海关编码

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Targets
Mechanism
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Animal study
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1: Zheng Y, Nandakumar KS, Cheng K. Optimization of CAR-T Cell-Based Therapies Using Small-Molecule-Based Safety Switches. J Med Chem. 2021 Jul 22;64(14):9577-9591. doi: 10.1021/acs.jmedchem.0c02054. Epub 2021 Jun 30. PMID: 34191515.

2: Warda W, Da Rocha MN, Trad R, Haderbache R, Salma Y, Bouquet L, Roussel X, Nicod C, Deschamps M, Ferrand C. Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch. Cancer Gene Ther. 2021 Dec;28(12):1365-1375. doi: 10.1038/s41417-020-00284-3. Epub 2021 Jan 7. PMID: 33414517; PMCID: PMC8636256.

3: Amatya C, Pegues MA, Lam N, Vanasse D, Geldres C, Choi S, Hewitt SM, Feldman SA, Kochenderfer JN. Development of CAR T Cells Expressing a Suicide Gene Plus a Chimeric Antigen Receptor Targeting Signaling Lymphocytic-Activation Molecule F7. Mol Ther. 2021 Feb 3;29(2):702-717. doi: 10.1016/j.ymthe.2020.10.008. Epub 2020 Oct 14. PMID: 33129371; PMCID: PMC7854354.

4: Wang X, Jasinski DL, Medina JL, Spencer DM, Foster AE, Bayle JH. Inducible MyD88/CD40 synergizes with IL-15 to enhance antitumor efficacy of CAR-NK cells. Blood Adv. 2020 May 12;4(9):1950-1964. doi: 10.1182/bloodadvances.2020001510. PMID: 32384544; PMCID: PMC7218419.

5: Duong MT, Collinson-Pautz MR, Morschl E, Lu A, Szymanski SP, Zhang M, Brandt ME, Chang WC, Sharp KL, Toler SM, Slawin KM, Foster AE, Spencer DM, Bayle JH. Two-Dimensional Regulation of CAR-T Cell Therapy with Orthogonal Switches. Mol Ther Oncolytics. 2018 Dec 20;12:124-137. doi: 10.1016/j.omto.2018.12.009. PMID: 30740516; PMCID: PMC6357218.

6: Warda W, Larosa F, Neto Da Rocha M, Trad R, Deconinck E, Fajloun Z, Faure C, Caillot D, Moldovan M, Valmary-Degano S, Biichle S, Daguindau E, Garnache-Ottou F, Tabruyn S, Adotevi O, Deschamps M, Ferrand C. CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor-Engineered T Cells. Cancer Res. 2019 Feb 1;79(3):663-675. doi: 10.1158/0008-5472.CAN-18-1078. Epub 2018 Dec 4. PMID: 30514753.

7: Foster AE, Mahendravada A, Shinners NP, Chang WC, Crisostomo J, Lu A, Khalil M, Morschl E, Shaw JL, Saha S, Duong MT, Collinson-Pautz MR, Torres DL, Rodriguez T, Pentcheva-Hoang T, Bayle JH, Slawin KM, Spencer DM. Regulated Expansion and Survival of Chimeric Antigen Receptor-Modified T Cells Using Small Molecule-Dependent Inducible MyD88/CD40. Mol Ther. 2017 Sep 6;25(9):2176-2188. doi: 10.1016/j.ymthe.2017.06.014. Epub 2017 Jul 8. PMID: 28697888; PMCID: PMC5589084.

8: Sonpavde G, McMannis JD, Bai Y, Seethammagari MR, Bull JMC, Hawkins V, Dancsak TK, Lapteva N, Levitt JM, Moseley A, Spencer DM, Slawin KM. Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer. Cancer Immunol Immunother. 2017 Oct;66(10):1345-1357. doi: 10.1007/s00262-017-2027-6. Epub 2017 Jun 12. PMID: 28608115; PMCID: PMC11029714.

9: Zhou X, Dotti G, Krance RA, Martinez CA, Naik S, Kamble RT, Durett AG, Dakhova O, Savoldo B, Di Stasi A, Spencer DM, Lin YF, Liu H, Grilley BJ, Gee AP, Rooney CM, Heslop HE, Brenner MK. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015 Jun 25;125(26):4103-13. doi: 10.1182/blood-2015-02-628354. Epub 2015 May 14. PMID: 25977584; PMCID: PMC4481597.

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Rimiducid

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