Rimiducid | CAS#195514-63-7 | MedKoo Biosciences

MedKoo Cat#: 205899 | Name: Rimiducid

Description:

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

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.

Chemical Structure

Rimiducid

CAS#195514-63-7

Theoretical Analysis

MedKoo Cat#: 205899

Name: Rimiducid

CAS#: 195514-63-7

Chemical Formula: C78H98N4O20

Exact Mass: 1410.6774

Molecular Weight: 1411.65

Elemental Analysis: C, 66.37; H, 7.00; N, 3.97; O, 22.67

Price and Availability

Size	Price	Availability
5mg	USD 210.00	Ready to ship
10mg	USD 350.00	Ready to ship
25mg	USD 750.00	Ready to ship
50mg	USD 1,250.00	Ready to ship
100mg	USD 2,250.00	Ready to ship
200mg	USD 4,050.00	Ready to ship

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Related CAS #

No Data

Synonym

AP1903; AP 1903; AP-1903; Rimiducid;

IUPAC/Chemical Name

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)-

InChi Key

GQLCLPLEEOUJQC-ZTQDTCGGSA-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

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

Appearance

Semisolid (wax like)

Purity

>92% (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 ARGENTÂ™ 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).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A22T12K07

QC Data

View QC data: current batch, Lot#A22T12K07

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

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.