CALCITRIOL

ID: ALA846

Max Phase: Approved

First Approval: 1978

Molecular Formula: C27H44O3

Molecular Weight: 416.65

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (9): 1,25-dihydroxy vitamin d3 | 1,25-dihydroxyvitamin d3 | 1,25-hydroxylated vitamin d | 1alpha,25-dihydroxycholecalciferol | 1alpha,25-dihydroxyvitamin d3 | Calcitriol | RO 21-5535 | RO-21-5535 | RO-215535
Synonyms from Alternative Forms(9):

    Trade Names(8): Calcijex | Calcitriol | Dihydroxycholecalciferol | Dihydroxyvitamin D 3 | Rocaltrol | Silkis | Topitriol | Vectical

    Canonical SMILES:  C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)CCCC(C)(C)O)CC[C@@H]23)C[C@@H](O)C[C@@H]1O

    Standard InChI:  InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1

    Standard InChI Key:  GMRQFYUYWCNGIN-NKMMMXOESA-N

    Associated Targets(Human)

    RWLeu4 20 Activities

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    U-937 7138 Activities

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    HL-60 67320 Activities

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    Vitamin D receptor 26531 Activities

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    Homo sapiens 32628 Activities

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    Vitamin D-binding protein 57 Activities

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    MG-63 795 Activities

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    MCF7 126967 Activities

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    PBMC 10003 Activities

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    LNCaP 8286 Activities

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    NB-4 999 Activities

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    Histone deacetylase 6747 Activities

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    Microtubule-associated protein tau 95507 Activities

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    MAP kinase ERK2 25055 Activities

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    Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 93046 Activities

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    A498 42825 Activities

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    Ubiquitin carboxyl-terminal hydrolase 1 22556 Activities

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    T47D 39041 Activities

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    HaCaT 4069 Activities

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    Geminin 128009 Activities

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    HCT-116 91556 Activities

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    T98G 1524 Activities

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    Retinoic acid receptor 39 Activities

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    Glucocorticoid receptor 14987 Activities

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    Retinoid X receptor 114 Activities

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    Androgen Receptor 11781 Activities

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    Tyrosyl-DNA phosphodiesterase 1 345557 Activities

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    HEK293 82097 Activities

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    Cytochrome P450 24A1 161 Activities

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    Liver microsome 8277 Activities

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    HepG2 196354 Activities

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    Bile salt export pump 2311 Activities

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    Canalicular multispecific organic anion transporter 1 1191 Activities

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    Canalicular multispecific organic anion transporter 2 718 Activities

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    Multidrug resistance-associated protein 4 785 Activities

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    PC-3 62116 Activities

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    Caco-2 12174 Activities

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    L02 4864 Activities

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    SK-OV-3 52876 Activities

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    BXPC-3 2997 Activities

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    Retinoic acid receptor RXR-alpha/Vitamin D3 receptor 15 Activities

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    Histone deacetylase 6 20808 Activities

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    SW480 6023 Activities

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    HERG 29587 Activities

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    Beta-1 adrenergic receptor 6630 Activities

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    Beta-2 adrenergic receptor 11824 Activities

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    Dopamine transporter 10535 Activities

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    Neuronal acetylcholine receptor protein alpha-4 subunit 1265 Activities

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    Kappa opioid receptor 16155 Activities

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    Serotonin 2c (5-HT2c) receptor 11471 Activities

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    Adenosine A1 receptor 17603 Activities

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    Adenosine A3 receptor 15931 Activities

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    Muscarinic acetylcholine receptor M1 12690 Activities

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    Muscarinic acetylcholine receptor M3 7750 Activities

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    Alpha-1a adrenergic receptor 8359 Activities

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    Dopamine D2 receptor 23596 Activities

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    Equilibrative nucleoside transporter 1 1711 Activities

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    Alpha-2b adrenergic receptor 4412 Activities

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    Norepinephrine transporter 10102 Activities

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    Mu opioid receptor 19785 Activities

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    Alpha-2c adrenergic receptor 4876 Activities

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    Serotonin 3a (5-HT3a) receptor 3366 Activities

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    Serotonin transporter 12625 Activities

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    Adenosine A2a receptor 16305 Activities

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    Delta opioid receptor 15096 Activities

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    Thromboxane A2 receptor 5717 Activities

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    Monoamine oxidase A 11911 Activities

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    Vasopressin V1a receptor 5412 Activities

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    Vasopressin V2 receptor 2912 Activities

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    Cyclooxygenase-2 13999 Activities

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    Estrogen receptor alpha 17718 Activities

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    Histamine H2 receptor 5428 Activities

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    Bradykinin B2 receptor 3970 Activities

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    Cholecystokinin B receptor 3550 Activities

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    Ghrelin receptor 6229 Activities

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    Type-1 angiotensin II receptor 5176 Activities

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    Cholecystokinin A receptor 4460 Activities

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    Dopamine D1 receptor 9720 Activities

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    Cannabinoid CB1 receptor 20913 Activities

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    Melanocortin receptor 3 5659 Activities

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    Melanocortin receptor 4 10016 Activities

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    Phosphodiesterase 4D 3546 Activities

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    Neuropeptide Y receptor type 1 5019 Activities

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    Pregnane X receptor 6667 Activities

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    Motilin receptor 1724 Activities

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    Phosphodiesterase 3A 3309 Activities

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    Dopamine D3 receptor 14368 Activities

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    Histamine H3 receptor 10389 Activities

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    Histamine H1 receptor 7573 Activities

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    Muscarinic acetylcholine receptor M2 10671 Activities

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    Serotonin 1a (5-HT1a) receptor 14969 Activities

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    Alpha-2a adrenergic receptor 9450 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Progesterone receptor 8562 Activities

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    Serotonin 2a (5-HT2a) receptor 14758 Activities

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    Serotonin 2b (5-HT2b) receptor 10323 Activities

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    HEK-293T 167025 Activities

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    U2OS 164939 Activities

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    Fibroblast 163371 Activities

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    Casein kinase I delta 4546 Activities

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    Cyclin-dependent kinase 2 9050 Activities

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    Glycogen synthase kinase-3 beta 11785 Activities

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    Serine/threonine-protein kinase Aurora-A 10240 Activities

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    Tyrosine-protein kinase ABL 18331 Activities

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    Fibroblast growth factor receptor 3 7811 Activities

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    Peregrin 2217 Activities

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    Transcription intermediary factor 1-alpha 2087 Activities

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    Bromodomain-containing protein 4 13122 Activities

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    Associated Targets(non-human)

    Vitamin D-binding protein 39 Activities

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    Vitamin D receptor 379 Activities

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    Rattus norvegicus 775804 Activities

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    Vitamin D receptor 183 Activities

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    Vitamin D receptor 148 Activities

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    Vitamin D3 receptor 18 Activities

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    Mus musculus 284745 Activities

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    Vitamin D3 receptor 135 Activities

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    Gallus gallus 1187 Activities

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    C3H 10T1/2 488 Activities

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    Liver microsomes 8692 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kidney 678 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Nuclear receptor ROR-gamma 89407 Activities

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    Thioredoxin glutathione reductase 28579 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Ferritin light chain 43324 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Vitamin D receptor 250 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Peripheral myelin protein 22 1279 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Vitamin D3 receptor A 38 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SARS-CoV-2 38078 Activities

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    Replicase polyprotein 1ab 11336 Activities

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    Candida albicans 78123 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cryptococcus neoformans 21258 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Escherichia coli 133304 Activities

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    Klebsiella pneumoniae 43867 Activities

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    Pseudomonas aeruginosa 123386 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Acinetobacter baumannii 41033 Activities

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    Staphylococcus aureus 210822 Activities

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    Voltage-gated L-type calcium channel alpha-1C subunit 1321 Activities

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    Glutamate (NMDA) receptor subunit zeta 1 2166 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    GABA receptor alpha-1 subunit 2848 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cyclooxygenase-1 1373 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Androgen Receptor 5522 Activities

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    Molecule Features

    Natural Product: NoOral: YesChemical Probe: NoParenteral: Yes
    Molecule Type: Small moleculeTopical: YesFirst In Class: NoBlack Box: No
    Chirality: YesAvailability: YesProdrug: No

    Drug Indications

    MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

    Mechanisms of Action

    Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

    Properties

    Molecular Weight: 416.65Molecular Weight (Monoisotopic): 416.3290AlogP: 5.70#Rotatable Bonds: 6
    Polar Surface Area: 60.69Molecular Species: NEUTRALHBA: 3HBD: 3
    #RO5 Violations: 1HBA (Lipinski): 3HBD (Lipinski): 3#RO5 Violations (Lipinski): 1
    CX Acidic pKa: CX Basic pKa: CX LogP: 4.35CX LogD: 4.35
    Aromatic Rings: 0Heavy Atoms: 30QED Weighted: 0.52Np Likeness Score: 2.65

    References

    1. Yamamoto K, Ooizumi H, Umesono K, Verstuyf A, Bouillon R, DeLuca HF, Shinki T, Suda T, Yamada S..  (1999)  Three-dimensional structure-function relationship of vitamin D: side chain location and various activities.,  (7): [PMID:10230636] [10.1016/s0960-894x(99)00129-8]
    2. Suhara Y, Nihei KI, Tanigawa H, Fujishima T, Konno K, Nakagawa K, Okano T, Takayama H..  (2000)  Syntheses and biological evaluation of novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues.,  10  (10): [PMID:10843234] [10.1016/s0960-894x(00)00189-x]
    3. Yamada S, Yamamoto K, Naito H, Suzuki T, Ohmori M, Takayama H, Shiina Y, Miyaura C, Tanaka H, Abe E..  (1985)  Syntheses and differentiating action of vitamin D endoperoxides. Singlet oxygen adducts of vitamin D derivatives in human myeloid leukemia cells (HL-60).,  28  (9): [PMID:2993611] [10.1021/jm00147a005]
    4. Ono Y, Watanabe H, Akira K, Kubodera N, Okano T, Tsugawa N, Kobayashi T.  (1994)  Synthesis and biological character of 1-hydroxylated vitamin D3 Analogues,  (12): [10.1016/S0960-894X(01)80525-4]
    5. Konno K, Maki S, Fujishima T, Liu Z, Miura D, Chokki M, Takayama H..  (1998)  A novel and practical route to A-ring enyne synthon for 1 alpha,25-dihydroxyvitamin D3 analogs: synthesis of A-ring diastereomers of 1 alpha,25-dihydroxyvitamin D2 and 3-methyl-1,25-dihydroxyvitamin D3.,  (2): [PMID:9871644] [10.1016/s0960-894x(97)10204-9]
    6. Wu Y, Sabbe K, De Clercq P, Vandewalle M, Bouillon R, Verstuyf A..  (2002)  Vitamin D(3): synthesis of seco C-9,11,21-trisnor-17-methyl-1 alpha, 25-dihydroxyvitamin D(3) analogues.,  12  (12): [PMID:12039578] [10.1016/s0960-894x(02)00221-4]
    7. Wu Y, De Clercq P, Vandewalle M, Bouillon R, Verstuyf A..  (2002)  Vitamin D(3): synthesis of seco-C-9,11-bisnor-17-methyl-1 alpha,25-dihydroxyvitamin D(3) analogues.,  12  (12): [PMID:12039579] [10.1016/s0960-894x(02)00222-6]
    8. Posner GH, Halford BA, Peleg S, Dolan P, Kensler TW..  (2002)  Conceptually new low-calcemic oxime analogues of the hormone 1 alpha,25-dihydroxyvitamin D(3): synthesis and biological testing.,  45  (8): [PMID:11931627] [10.1021/jm010560o]
    9. Kobayashi T, Okano T, Tsugawa N, Murano M, Masuda S, Takeuchi A, Sato K, Nishii Y.  (1993)  2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3 (ED-71), preventive and therapeutic effects on bone mineral loss in ovariectomized rats,  (9): [10.1016/S0960-894X(00)80111-0]
    10. Goff JP, Horst RL, Uskokovic M.  (1993)  1,25,28-trihydroxyvitamin D2 up-regulates renal vitamin D receptor without causing hypercalcemia,  (9): [10.1016/S0960-894X(00)80113-4]
    11. Masuno H, Yamamoto K, Wang X, Choi M, Ooizumi H, Shinki T, Yamada S..  (2002)  Rational design, synthesis, and biological activity of novel conformationally restricted vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24-didehydro-24a,24b-dihomo-20-epivitamin D(3).,  45  (9): [PMID:11960494] [10.1021/jm0105631]
    12. Posner GH, Guyton KZ, Kensler TW, Barsony J, Lieberman ME, Reddy G, Clark JW, Wankadiya KF, Tserng K.  (1993)  1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation,  (9): [10.1016/S0960-894X(00)80115-8]
    13. Calverley MJ, Binderup L.  (1993)  Synthesis and biological evaluation of MC 1357, a new 20-epi-23-oxa-1,25-dihydroxy-vitamin D3 analogue with potent non-classical effects,  (9): [10.1016/S0960-894X(00)80117-1]
    14. Binderup L.  (1993)  Vitamin D analogues: new regulators of cancer cell growth and differentiation,  (9): [10.1016/S0960-894X(00)80126-2]
    15. Fujishima T, Liu Z, Miura D, Chokki M, Ishizuka S, Konno K, Takayama H..  (1998)  Synthesis and biological activity of 2-methyl-20-epi analogues of 1 alpha,25-dihydroxyvitamin D3.,  (16): [PMID:9873502] [10.1016/s0960-894x(98)00363-1]
    16. Posner GH, Lee JK, Li Z, Takeuchi K, Guggino SE, Dolan P, Kensler TW.  (1995)  1,25-Dihydroxyvitamin D3 Hybrid Analogs with Structural changes at both the A-ring and the C,D-ring side-chain. II,  (18): [10.1016/0960-894X(95)00376-5]
    17. Maynard DF, Trankle WG, Norman AW, Okamura WH..  (1994)  14-epi stereoisomers of 25-hydroxy- and 1 alpha,25-dihydroxyvitamin D3: synthesis, isomerization to previtamins, and biological studies.,  37  (15): [PMID:8057286] [10.1021/jm00041a017]
    18. Figadère B, Norman AW, Henry HL, Koeffler HP, Zhou JY, Okamura WH..  (1991)  Arocalciferols: synthesis and biological evaluation of aromatic side-chain analogues of 1 alpha,25-dihydroxyvitamin D3(1a).,  34  (8): [PMID:1652020] [10.1021/jm00112a021]
    19. Norman AW, Manchand PS, Uskokovic MR, Okamura WH, Takeuchi JA, Bishop JE, Hisatake JI, Koeffler HP, Peleg S..  (2000)  Characterization of a novel analogue of 1alpha,25(OH)(2)-vitamin D(3) with two side chains: interaction with its nuclear receptor and cellular actions.,  43  (14): [PMID:10893309] [10.1021/jm0000160]
    20. Yamamoto K, Sun WY, Ohta M, Hamada K, DeLuca HF, Yamada S..  (1996)  Conformationally restricted analogs of 1 alpha, 25-dihydroxyvitamin D3 and its 20-epimer: compounds for study of the three-dimensional structure of vitamin D responsible for binding to the receptor.,  39  (14): [PMID:8709103] [10.1021/jm9600048]
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