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.
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
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 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
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 human fibrosarcoma line HT1080 is engineered to express stably a fusion protein comprising a myristoylation sequence, two copies of F36V-FKBP, and the human first apoptosis signal (Fas) intracellular domain. Rimiducid (AP1903) elicits potent and dose-dependent apoptotic death of these engineered cells in culture, with an EC50 of ≈0.1 nM. Maximal killing occurred in the presence of 3 to 10 nM Rimiducid (AP1903), and the IC50 is approximately 0.2 nM. LV′VFas-transduced T lymphocytes expressing high levels of CD25 (top panel) are eliminated by with 66%±7.5% (n=10) efficiency. When cells are examined after CD25 expression returned to basal levels, 63%±4.7% (n=9) killing is observed after Rimiducid treatment.
Rimiducid (AP1903; i.v.,0.01, 0.1, 1, 10, and 100 mg/kg) elicits a dose-dependent decrease in serum human GH levels, with a half-maximal effective dose of 0.4±0.1 mg/kg.
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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.
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.
Sadelain M. Eliminating cells gone astray. N Engl J Med. 2011 Nov 3;365(18):1735-7. doi: 10.1056/NEJMe1109971. PubMed PMID: 22047566.
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