WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205899
CAS#: 195514-63-7
Description: AP1903, also known as Rimiducid, is a lipid-permeable tacrolimus analogue with homodimerizing activity. Dimerizer drug AP1903 homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val) so that AP1903 binds to wild-type FKBP12 with 1000-fold lower affinity. This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered receptors such as the iCD40 receptor of the autologous dendritic cell vaccine BP-GMAX-CD1, resulting in receptor activation.
MedKoo Cat#: 205899
Name: AP1903
CAS#: 195514-63-7
Chemical Formula: C78H98N4O20
Exact Mass: 1410.67744
Molecular Weight: 1411.63
Elemental Analysis: C, 66.37; H, 7.00; N, 3.97; O, 22.67
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
The following data is based on the product molecular weight 1411.63 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 |
1: 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 May 14. pii: blood-2015-02-628354. [Epub ahead of print] PubMed PMID: 25977584.
2: 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. eCollection 2014. Review. PubMed PMID: 25389405; PubMed Central PMCID: PMC4211380.
3: 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. PubMed PMID: 25330775; PubMed Central PMCID: PMC4270878.
4: 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. PubMed PMID: 24753538; PubMed Central PMCID: PMC4064331.
5: Sadelain M. Eliminating cells gone astray. N Engl J Med. 2011 Nov 3;365(18):1735-7. doi: 10.1056/NEJMe1109971. PubMed PMID: 22047566.
6: Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, Liu H, Cruz CR, Savoldo B, Gee AP, Schindler J, Krance RA, Heslop HE, Spencer DM, Rooney CM, Brenner MK. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011 Nov 3;365(18):1673-83. doi: 10.1056/NEJMoa1106152. PubMed PMID: 22047558; PubMed Central PMCID: PMC3236370.
7: Narayanan P, Lapteva N, Seethammagari M, Levitt JM, Slawin KM, Spencer DM. A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy. J Clin Invest. 2011 Apr;121(4):1524-34. doi: 10.1172/JCI44327. Epub 2011 Mar 7. PubMed PMID: 21383499; PubMed Central PMCID: PMC3069772.
8: Okazuka K, Beard BC, Emery DW, Schwarzwaelder K, Spector MR, Sale GE, von Kalle C, Torok-Storb B, Kiem HP, Blau CA. Long-term regulation of genetically modified primary hematopoietic cells in dogs. Mol Ther. 2011 Jul;19(7):1287-94. doi: 10.1038/mt.2011.8. Epub 2011 Feb 15. Erratum in: Mol Ther. 2011 Nov;19(11):2102. Torok-Storb, Beverly [added]. PubMed PMID: 21326218; PubMed Central PMCID: PMC3129573.
9: Lapteva N. Enhanced migration of human dendritic cells expressing inducible CD40. Methods Mol Biol. 2010;651:79-87. doi: 10.1007/978-1-60761-786-0_5. PubMed PMID: 20686961.
10: Miller CP, Blau CA. Using gene transfer to circumvent off-target effects. Gene Ther. 2008 May;15(10):759-64. doi: 10.1038/gt.2008.43. Epub 2008 Mar 20. Review. PubMed PMID: 18356813.
AP1903 was discovered and developed by ARIAD scientists, as a part of ARIAD’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).
