Rimiducid
new
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205899

CAS#: 195514-63-7

Description: 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.

Chemical Structure

img
Rimiducid
CAS# 195514-63-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205899
Name: Rimiducid
CAS#: 195514-63-7
Chemical Formula: C78H98N4O20
Exact Mass: 1,410.68
Molecular Weight: 1,411.650
Elemental Analysis: C, 66.37; H, 7.00; N, 3.97; O, 22.67

Price and Availability

Size Price Availability Quantity
5mg USD 210 Ready to ship
10mg USD 350 Ready to ship
25mg USD 750 Ready to ship
50mg USD 1250 Ready to ship
100mg USD 2250 Ready to ship
200mg USD 4050 Ready to ship
Bulk inquiry

Synonym: AP1903; AP 1903; AP-1903; Rimiducid;

IUPAC/Chemical Name: (S,2R,2'R)-(1R,1'R)-((((ethane-1,2-diylbis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(oxy))bis(3,1-phenylene))bis(3-(3,4-dimethoxyphenyl)propane-1,1-diyl) bis(1-((S)-2-(3,4,5-trimethoxyphenyl)butanoyl)piperidine-2-carboxylate)

InChi Key: GQLCLPLEEOUJQC-WFMNNBDOSA-N

InChi Code: 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

SMILES Code: O=C(NCCNC(COC1=CC([C@H](OC([C@H]2CCCCN2C([C@H](C3=CC(OC)=C(OC)C(OC)=C3)CC)=O)=O)CCC4=CC=C(OC)C(OC)=C4)=CC=C1)=O)COC5=CC([C@H](OC([C@H]6CCCCN6C([C@@H](CC)C7=CC(OC)=C(OC)C(OC)=C7)=O)=O)CCC8=CC=C(OC)C(OC)=C8)=CC=C5.

Appearance: Semisolid (wax like)

Purity: >95% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: AP1903 was discovered and developed by ARIAD scientists, as a part of ARIADÂ’s ARGENT™ technology platform which combines chemistry and genetics to allow specific cell-signaling and gene-expression events to be chemically activated in whole animals and cultured cells. The technology platform includes a portfolio of distinct small-molecule "dimerizer" compounds optimized for specific applications. Dimerizers bring specific proteins together in cells.   (source: http://www.ariad.com/wt/tertiarypage/AP1903).         

Biological target: Rimiducid (AP1903) is a dimerizer agent that acts by cross-linking the FKBP domains.
In vitro activity: The induction of iCasp9 depends on the administration of the small molecule dimerizer drug AP1903 and dimerization results in rapid induction of apoptosis in transduced cells, preferentially killing activated cells expressing high levels of transgene. Reference: Front Pharmacol. 2014 Oct 28;5:235. https://pubmed.ncbi.nlm.nih.gov/25389405/
In vivo activity: Over 3 consecutive days, this study implanted these cells i.m. into nude mice, treated the animals i.v. with various doses of AP1903, and then determined serum hGH levels as a measure of the number of surviving cells. Fig. Fig.5B shows that AP1903 elicited a dose-dependent decrease in serum hGH levels, with a half-maximal effective dose of 0.4 ± 0.1 mg/kg. Thus, the bumped dimerizer retains potent activity in vivo, indicating that the remodeled interface is functional in a whole animal context. Reference: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42. https://pubmed.ncbi.nlm.nih.gov/9724721/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 97.1 68.75
Ethanol 120.6 85.42

Preparing Stock Solutions

The following data is based on the product molecular weight 1,411.65 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014 Oct 28;5:235. doi: 10.3389/fphar.2014.00235. PMID: 25389405; PMCID: PMC4211380. 2. Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M, Bordignon C, Clackson T. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood. 2001 Mar 1;97(5):1249-57. doi: 10.1182/blood.v97.5.1249. PMID: 11222367. 3. 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. 4. Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, Stevenson LF, Magari SR, Wood SA, Courage NL, Lu X, Cerasoli F Jr, Gilman M, Holt DA. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42. doi: 10.1073/pnas.95.18.10437. PMID: 9724721; PMCID: PMC27912.
In vitro protocol: 1. Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014 Oct 28;5:235. doi: 10.3389/fphar.2014.00235. PMID: 25389405; PMCID: PMC4211380. 2. Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M, Bordignon C, Clackson T. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood. 2001 Mar 1;97(5):1249-57. doi: 10.1182/blood.v97.5.1249. PMID: 11222367.
In vivo protocol: 1. 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. 2. Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, Stevenson LF, Magari SR, Wood SA, Courage NL, Lu X, Cerasoli F Jr, Gilman M, Holt DA. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10437-42. doi: 10.1073/pnas.95.18.10437. PMID: 9724721; PMCID: PMC27912.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Lin RJ, Nager AR, Park S, Sutton J, Lay C, Melton Z, Zhang Y, Boldajipour B, Blarcom TJV, Panowski SH, Sasu BJ, Chaparro-Riggers J. Design and Validation of Inducible TurboCARs with Tunable Induction and Combinatorial Cytokine Signaling. Cancer Immunol Res. 2022 Sep 1;10(9):1069-1083. doi: 10.1158/2326-6066.CIR-21-0253. PMID: 35881865.


2: Romecín PA, Vinyoles M, López-Millán B, de la Guardia RD, Atucha NM, Querol S, Bueno C, Benitez R, Gonzalez-Rey E, Delgado M, Menéndez P. Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell. Stem Cells Transl Med. 2022 Mar 3;11(1):88-96. doi: 10.1093/stcltm/szab007. PMID: 35641173; PMCID: PMC8895490.


3: Liu Y, Yang Y, Suo Y, Li C, Chen M, Zheng S, Li H, Tang C, Fan N, Lan T, Zhou J, Li Y, Wang J, Chen H, Zou Q, Lai L. Inducible caspase-9 suicide gene under control of endogenous oct4 to safeguard mouse and human pluripotent stem cell therapy. Mol Ther Methods Clin Dev. 2022 Feb 1;24:332-341. doi: 10.1016/j.omtm.2022.01.014. PMID: 35229007; PMCID: PMC8851157.


4: Guercio M, Manni S, Boffa I, Caruso S, Di Cecca S, Sinibaldi M, Abbaszadeh Z, Camera A, Ciccone R, Polito VA, Ferrandino F, Reddel S, Catanoso ML, Bocceri E, Del Bufalo F, Algeri M, De Angelis B, Quintarelli C, Locatelli F. Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies. Front Immunol. 2021 Oct 19;12:755639. doi: 10.3389/fimmu.2021.755639. PMID: 34737753; PMCID: PMC8560965.


5: Madadi Z, Akbari-Birgani S, Mohammadi S, Khademy M, Mousavi SA. The effect of caspase-9 in the differentiation of SH-SY5Y cells. Eur J Pharmacol. 2021 Aug 5;904:174138. doi: 10.1016/j.ejphar.2021.174138. Epub 2021 Apr 30. PMID: 33933463.


6: Mashima H, Zhang R, Kobayashi T, Tsukamoto H, Liu T, Iwama T, Hagiya Y, Yamamoto M, Fukushima S, Okada S, Idiris A, Kaneko S, Nakatsura T, Ohdan H, Uemura Y. Improved safety of induced pluripotent stem cell-derived antigen- presenting cell-based cancer immunotherapy. Mol Ther Methods Clin Dev. 2021 Mar 5;21:171-179. doi: 10.1016/j.omtm.2021.03.002. PMID: 33816647; PMCID: PMC7994724.


7: 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.


8: Shi ZD, Tchao J, Wu L, Carman AJ. Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells. Stem Cells Transl Med. 2020 Nov;9(11):1378-1388. doi: 10.1002/sctm.20-0007. Epub 2020 Jul 13. PMID: 32662231; PMCID: PMC7581441.


9: Wu Y, Chang T, Long Y, Huang H, Kandeel F, Yee JK. Using Gene Editing to Establish a Safeguard System for Pluripotent Stem-Cell-Based Therapies. iScience. 2019 Dec 20;22:409-422. doi: 10.1016/j.isci.2019.11.038. Epub 2019 Nov 25. PMID: 31821946; PMCID: PMC6909005.


10: Minagawa K, Al-Obaidi M, Di Stasi A. Generation of Suicide Gene-Modified Chimeric Antigen Receptor-Redirected T-Cells for Cancer Immunotherapy. Methods Mol Biol. 2019;1895:57-73. doi: 10.1007/978-1-4939-8922-5_5. PMID: 30539529.


11: 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.


12: Bôle-Richard E, Gamonet C, Certoux JM, Idirene I, Larosa F, Deconinck E, Mosseley AM, Tiberghien P, Borg C, Ferrand C, Deschamps M. Exposure to hypomethylating agent, 5-azacytidine, may improve iCasp9 suicide gene therapy for treating GvHD in allografts. Gene Ther. 2016 Aug;23(8-9):664-72. doi: 10.1038/gt.2016.39. Epub 2016 May 12. PMID: 27111151.


13: Zhou X, Naik S, Dakhova O, Dotti G, Heslop HE, Brenner MK. Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation. Mol Ther. 2016 Apr;24(4):823-31. doi: 10.1038/mt.2015.234. Epub 2015 Dec 28. PMID: 26708005; PMCID: PMC4886936.


14: Chang EC, Liu H, West JA, Zhou X, Dakhova O, Wheeler DA, Heslop HE, Brenner MK, Dotti G. Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch. Mol Ther. 2016 Apr;24(4):736-45. doi: 10.1038/mt.2015.217. Epub 2015 Dec 7. PMID: 26639404; PMCID: PMC4886929.


15: Zhou X, Di Stasi A, Brenner MK. iCaspase 9 Suicide Gene System. Methods Mol Biol. 2015;1317:87-105. doi: 10.1007/978-1-4939-2727-2_6. PMID: 26072403; PMCID: PMC4903016.


16: 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.


17: Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014 Oct 28;5:235. doi: 10.3389/fphar.2014.00235. PMID: 25389405; PMCID: PMC4211380.


18: Barese CN, Felizardo TC, Sellers SE, Keyvanfar K, Di Stasi A, Metzger ME, Krouse AE, Donahue RE, Spencer DM, Dunbar CE. Regulated apoptosis of genetically modified hematopoietic stem and progenitor cells via an inducible caspase-9 suicide gene in rhesus macaques. Stem Cells. 2015 Jan;33(1):91-100. doi: 10.1002/stem.1869. PMID: 25330775; PMCID: PMC4270878.


19: Ando M, Hoyos V, Yagyu S, Tao W, Ramos CA, Dotti G, Brenner MK, Bouchier- Hayes L. Bortezomib sensitizes non-small cell lung cancer to mesenchymal stromal cell-delivered inducible caspase-9-mediated cytotoxicity. Cancer Gene Ther. 2014 Nov;21(11):472-482. doi: 10.1038/cgt.2014.53. Epub 2014 Oct 17. PMID: 25323693; PMCID: PMC4245333.


20: Zhou X, Di Stasi A, Tey SK, Krance RA, Martinez C, Leung KS, Durett AG, Wu MF, Liu H, Leen AM, Savoldo B, Lin YF, Grilley BJ, Gee AP, Spencer DM, Rooney CM, Heslop HE, Brenner MK, Dotti G. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood. 2014 Jun 19;123(25):3895-905. doi: 10.1182/blood-2014-01-551671. Epub 2014 Apr 21. PMID: 24753538; PMCID: PMC4064331.