(4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile
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Overview
- DrugBank ID
- DB07242
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 0
- Phase 2
- 0
- Phase 3
- 0
- Phase 4
- 0
Identification
- Generic Name
- (4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrile
- DrugBank Accession Number
- DB07242
- Background
Not Available
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 377.268
Monoisotopic: 376.085766632 - Chemical Formula
- C18H18Cl2N4O
- Synonyms
- Not Available
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism UDeath-associated protein kinase 3 Not Available Humans USerine/threonine-protein kinase pim-1 Not Available Humans - 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. View sample adverse effects data in our new Data Library!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
- Not Available
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as beta carbolines. These are compounds containing a 9H-pyrido[3,4-b]indole moiety.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Pyridoindoles
- Direct Parent
- Beta carbolines
- Alternative Parents
- Indolecarboxylic acids and derivatives / 3-alkylindoles / N-alkylindoles / 2-heteroaryl carboxamides / Aralkylamines / Piperidines / Aryl chlorides / N-methylpyrroles / Benzenoids / Heteroaromatic compounds show 11 more
- Substituents
- 2-heteroaryl carboxamide / 3-alkylindole / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid show 26 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- XGUIMGJMQKZRGM-LLVKDONJSA-N
- InChI
- InChI=1S/C18H18Cl2N4O/c1-23-7-5-18(6-8-23)11(9-21)13-10-3-4-12(19)14(20)15(10)24(2)16(13)17(25)22-18/h3-4,11H,5-8H2,1-2H3,(H,22,25)/t11-/m1/s1
- IUPAC Name
- (4'R)-7',8'-dichloro-1,9'-dimethyl-1'-oxo-1',2',4',9'-tetrahydrospiro[piperidine-4,3'-pyrido[3,4-b]indole]-4'-carbonitrile
- SMILES
- [H][C@@]1(C#N)C2=C(N(C)C3=C(Cl)C(Cl)=CC=C23)C(=O)NC11CCN(C)CC1
References
- General References
- Not Available
- External Links
- PubChem Compound
- 24851688
- PubChem Substance
- 99443713
- ChemSpider
- 25056752
- ZINC
- ZINC000024963803
- PDBe Ligand
- 7CP
- PDB Entries
- 3bhy / 3cxw
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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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 0.107 mg/mL ALOGPS logP 3.06 ALOGPS logP 1.93 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 12.87 Chemaxon pKa (Strongest Basic) 8.34 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 61.06 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 99.22 m3·mol-1 Chemaxon Polarizability 38.62 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.7577 Caco-2 permeable + 0.566 P-glycoprotein substrate Substrate 0.8335 P-glycoprotein inhibitor I Inhibitor 0.7015 P-glycoprotein inhibitor II Inhibitor 0.5705 Renal organic cation transporter Inhibitor 0.5568 CYP450 2C9 substrate Non-substrate 0.8246 CYP450 2D6 substrate Non-substrate 0.7195 CYP450 3A4 substrate Substrate 0.8256 CYP450 1A2 substrate Non-inhibitor 0.598 CYP450 2C9 inhibitor Non-inhibitor 0.6322 CYP450 2D6 inhibitor Non-inhibitor 0.7715 CYP450 2C19 inhibitor Non-inhibitor 0.6004 CYP450 3A4 inhibitor Inhibitor 0.752 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6931 Ames test Non AMES toxic 0.6447 Carcinogenicity Non-carcinogens 0.933 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.7667 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9403 hERG inhibition (predictor II) Inhibitor 0.6848
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-7e7ebb5e8130ee4bd853 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-0b81f7cd7c8e108276b0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-003r-8009000000-1df9debe2d058df7f942 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-309a3c6802880eb3dab5 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9004000000-5cae8092072cde1e1eaf Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000e-2029000000-4854ca6d56dbe38ff00d Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.68596 predictedDeepCCS 1.0 (2019) [M+H]+ 187.04396 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.62097 predictedDeepCCS 1.0 (2019)
Targets
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1. DetailsDeath-associated protein kinase 3
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor
- Specific Function
- ATP binding
- Gene Name
- DAPK3
- Uniprot ID
- O43293
- Uniprot Name
- Death-associated protein kinase 3
- Molecular Weight
- 52535.165 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
2. DetailsSerine/threonine-protein kinase pim-1
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15528381, PubMed:1825810, PubMed:31548394). Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3) (PubMed:18593906). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (By similarity). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (By similarity). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (By similarity). Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis (PubMed:19749799). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (PubMed:16356754). Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability (PubMed:12431783). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (PubMed:18593906). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (PubMed:18593906). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (PubMed:10664448). Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (By similarity). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (PubMed:37797010). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989). Promotes brown adipocyte differentiation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- PIM1
- Uniprot ID
- P11309
- Uniprot Name
- Serine/threonine-protein kinase pim-1
- Molecular Weight
- 35685.44 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Drug created at September 15, 2010 21:19 / Updated at June 12, 2020 16:52