Rimiducid
Identification
- Summary
Rimiducid is a homodimerizing agent potentially used in combination with cellular immunotherapies for cancers and blood disorders to increase the therapeutic effectiveness.
- Generic Name
- Rimiducid
- DrugBank Accession Number
- DB04974
- Background
Rimiducid is a lipid-permeable tacrolimus analogue and a protein dimerizer. It was designed to overcome limitations of current cellular immunotherapies used for cancer and other blood disorders by enhancing the control of the immune cell activity and function. When administered via chemically-inducible dimerization (CID) technologies, rimiducid binds to switch proteins and dimerizes them, triggering downstream signaling cascade.1,6 The combination use of rimiducid with immunotherapies for enhanced therapeutic effectiveness is currently under investigation.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 1411.65
Monoisotopic: 1410.677441572 - Chemical Formula
- C78H98N4O20
- Synonyms
- Rimiducid
- External IDs
- AP 1903
- AP-1903
- AP1903
Pharmacology
- Indication
Investigated for use/treatment in bone marrow transplant and graft versus host disease.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Rimiducis is used to activate inducible caspase-9 produced by a modified gene included in some CAR T-cell therapies.2,3 This activation produces rapid induction of apoptosis in activated modified T-cells and resolution of the signs and symptoms of graft versus host disease within 24 hours.4
- Mechanism of action
Rimiducid binds to a drug binding domain derived from human FK506-binding protein which is present on a modified form of inducible caspase-9.2 This binding results in dimerization and subsequent activation of caspase-9. This system was designed to function as a "safety switch" in CAR T-cell therapy used in hematological cancers. Retroviral vectors used in production of these modified cells preferentially integrate this gene nearby promoters associated with T-cell activation. This results in higher expression of the modified inducible caspase-9 product in activated T-cells. In practice, this allows for specific targeting of these active T-cells by rimiducid which results in a decrease in circulating cell numbers of over 90% in the setting of graft versus host disease. This specificity spares non-alloreactive T-cells and allows for successful reconstitution of the transplanted immune system from these cells.[24753538] Additionally, these non-alloreactive cells retain their sensitivity to rimiducid.
Target Actions Organism USerine/threonine-protein kinase mTOR ligandHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- H564L1W5J2
- CAS number
- 195514-63-7
- InChI Key
- 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
- IUPAC Name
- (1R)-3-(3,4-dimethoxyphenyl)-1-[3-({[2-(2-{3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyloxy]propyl]phenoxy}acetamido)ethyl]carbamoyl}methoxy)phenyl]propyl (2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate
- SMILES
- CC[C@H](C(=O)N1CCCC[C@H]1C(=O)O[C@H](CCC1=CC=C(OC)C(OC)=C1)C1=CC(OCC(=O)NCCNC(=O)COC2=CC=CC(=C2)[C@@H](CCC2=CC=C(OC)C(OC)=C2)OC(=O)[C@@H]2CCCCN2C(=O)[C@@H](CC)C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1)C1=CC(OC)=C(OC)C(OC)=C1
References
- General References
- DeRose R, Miyamoto T, Inoue T: Manipulating signaling at will: chemically-inducible dimerization (CID) techniques resolve problems in cell biology. Pflugers Arch. 2013 Mar;465(3):409-17. doi: 10.1007/s00424-012-1208-6. Epub 2013 Jan 9. [Article]
- Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, Heslop HE, Spencer DM, Rooney CM: An inducible caspase 9 safety switch for T-cell therapy. Blood. 2005 Jun 1;105(11):4247-54. doi: 10.1182/blood-2004-11-4564. Epub 2005 Feb 22. [Article]
- 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. [Article]
- 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. [Article]
- Definition of rimiducid - NCI Drug Dictionary - National Cancer Institute [Link]
- Technology - Bellicum Pharmaceuticals, Inc. [Link]
- External Links
- PubChem Substance
- 347909868
- ChemSpider
- 17292138
- ChEMBL
- CHEMBL269259
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.000397 mg/mL ALOGPS logP 6.88 ALOGPS logP 10.06 Chemaxon logS -6.6 ALOGPS pKa (Strongest Acidic) 14.34 Chemaxon pKa (Strongest Basic) -1.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 18 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 262.18 Å2 Chemaxon Rotatable Bond Count 39 Chemaxon Refractivity 379.49 m3·mol-1 Chemaxon Polarizability 153.98 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- General Function
- Tfiiic-class transcription factor binding
- Specific Function
- Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly...
- Gene Name
- MTOR
- Uniprot ID
- P42345
- Uniprot Name
- Serine/threonine-protein kinase mTOR
- Molecular Weight
- 288889.05 Da
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51