Identification
NameApatorsen
Accession NumberDB06094
TypeSmall Molecule
GroupsInvestigational
Description

Apatorsen is a second generation antisense drug which in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27) a cell survival protein found at elevated levels in many human cancers including prostate, lung, breast, ovarian, bladder, renal, pancreatic, multiple myeloma and liver cancer.

Structure
Thumb
SynonymsNot Available
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Apatorsen sodium3N4G7RE66Y 915443-09-3Not applicableDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIIFJ6X26JW6
CAS number1002331-21-6
WeightAverage: 7156.97
Monoisotopic: 7152.002582293
Chemical FormulaC224H304N79O116P19S19
InChI KeyRMTMMKNSPRRFHW-UHFFFAOYSA-N
InChI
InChI=1S/C224H304N79O116P19S19/c1-88-46-284(216(318)257-168(88)225)129-34-97(401-420(327,439)363-60-114-102(39-134(386-114)289-52-94(7)187(306)281-222(289)324)406-421(328,440)362-56-110-98(35-130(381-110)285-47-89(2)169(226)258-217(285)319)402-422(329,441)368-63-119-107(44-139(390-119)297-81-252-147-182(297)267-211(237)276-194(147)313)411-430(337,449)372-66-121-108(45-140(392-121)298-82-253-148-183(298)268-212(238)277-195(148)314)412-431(338,450)375-69-123-154(163(357-29-21-349-13)201(396-123)292-54-96(9)189(308)283-224(292)326)414-435(342,454)377-70-124-155(162(356-28-20-348-12)200(395-124)290-51-93(6)173(230)262-221(290)323)415-436(343,455)378-72-126-157(165(359-31-23-351-15)203(398-126)300-84-247-142-175(232)243-76-245-177(142)300)417-433(340,452)374-68-122-152(305)160(354-26-18-346-10)199(394-122)291-53-95(8)188(307)282-223(291)325)111(382-129)57-364-426(333,445)407-103-40-135(293-77-248-143-178(293)263-207(233)272-190(143)309)387-116(103)61-367-423(330,442)403-99-36-131(286-48-90(3)170(227)259-218(286)320)384-113(99)59-366-428(335,447)409-105-42-137(295-79-250-145-180(295)265-209(235)274-192(145)311)391-120(105)65-371-429(336,448)410-106-43-138(296-80-251-146-181(296)266-210(236)275-193(146)312)389-118(106)62-369-424(331,443)404-100-37-132(287-49-91(4)171(228)260-219(287)321)383-112(100)58-365-427(334,446)408-104-41-136(294-78-249-144-179(294)264-208(234)273-191(144)310)388-117(104)64-370-425(332,444)405-101-38-133(288-50-92(5)172(229)261-220(288)322)385-115(101)67-373-432(339,451)416-156-125(397-202(164(156)358-30-22-350-14)299-83-246-141-174(231)242-75-244-176(141)299)71-379-437(344,456)419-159-128(400-206(167(159)361-33-25-353-17)303-87-256-151-186(303)271-215(241)280-198(151)317)74-380-438(345,457)418-158-127(399-205(166(158)360-32-24-352-16)302-86-255-150-185(302)270-214(240)279-197(150)316)73-376-434(341,453)413-153-109(55-304)393-204(161(153)355-27-19-347-11)301-85-254-149-184(301)269-213(239)278-196(149)315/h46-54,75-87,97-140,152-167,199-206,304-305H,18-45,55-74H2,1-17H3,(H,327,439)(H,328,440)(H,329,441)(H,330,442)(H,331,443)(H,332,444)(H,333,445)(H,334,446)(H,335,447)(H,336,448)(H,337,449)(H,338,450)(H,339,451)(H,340,452)(H,341,453)(H,342,454)(H,343,455)(H,344,456)(H,345,457)(H2,225,257,318)(H2,226,258,319)(H2,227,259,320)(H2,228,260,321)(H2,229,261,322)(H2,230,262,323)(H2,231,242,244)(H2,232,243,245)(H,281,306,324)(H,282,307,325)(H,283,308,326)(H3,233,263,272,309)(H3,234,264,273,310)(H3,235,265,274,311)(H3,236,266,275,312)(H3,237,267,276,313)(H3,238,268,277,314)(H3,239,269,278,315)(H3,240,270,279,316)(H3,241,271,280,317)
IUPAC Name
SMILES
COCCOC1C(O)C(COP(O)(=S)OC2C(COP(O)(=S)OC3C(COP(O)(=S)OC4C(COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5CC(OC5COP(O)(=S)OC5C(COP(O)(=S)OC6C(COP(O)(=S)OC7C(COP(O)(=S)OC8C(CO)OC(C8OCCOC)N8C=NC9=C8NC(=N)N=C9O)OC(C7OCCOC)N7C=NC8=C7NC(=N)N=C8O)OC(C6OCCOC)N6C=NC7=C6NC(=N)N=C7O)OC(C5OCCOC)N5C=NC6=C(N)N=CN=C56)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=C(C)C(=N)N=C5O)N5C=C(C)C(O)=NC5=O)N5C=C(C)C(=N)N=C5O)N5C=NC6=C5NC(=N)N=C6O)N5C=NC6=C5NC(=N)N=C6O)OC(C4OCCOC)N4C=C(C)C(O)=NC4=O)OC(C3OCCOC)N3C=C(C)C(=N)N=C3O)OC(C2OCCOC)N2C=NC3=C(N)N=CN=C23)OC1N1C=C(C)C(O)=NC1=O
Pharmacology
Indication

Investigated for use/treatment in cancer/tumors (unspecified).

Structured Indications Not Available
Pharmacodynamics

OGX-427 significantly decreases levels of Hsp27, induces apoptosis in several human cancer cell lines, has single agent anti-tumor activity, and acts as a chemosensitizer in combination with several cytotoxic drugs including docetaxel.

Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
Heat shock protein beta-1ProteinunknownNot AvailableHumanP04792 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Kamada M, So A, Muramaki M, Rocchi P, Beraldi E, Gleave M: Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther. 2007 Jan;6(1):299-308. Epub 2007 Jan 11. [PubMed:17218637 ]
  2. Rocchi P, Jugpal P, So A, Sinneman S, Ettinger S, Fazli L, Nelson C, Gleave M: Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro. BJU Int. 2006 Nov;98(5):1082-9. Epub 2006 Jul 28. [PubMed:16879439 ]
  3. Zoubeidi A, Zardan A, Beraldi E, Fazli L, Sowery R, Rennie P, Nelson C, Gleave M: Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res. 2007 Nov 1;67(21):10455-65. [PubMed:17974989 ]
External LinksNot Available
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeoplasms1
1Unknown StatusTreatmentBladder Cancers1
2Active Not RecruitingTreatmentBladder Cancers / Transitional Cell Carcinoma1
2Active Not RecruitingTreatmentMalignant Neoplasm of Prostate / Metastatic Castrate-Resistant Prostate Cancer / PsA1
2Active Not RecruitingTreatmentNon Squamous Non Small Cell Lung Cancer1
2Active Not RecruitingTreatmentSquamous Cell Carcinoma of Lung1
2CompletedTreatmentCastration Resistant Prostate Cancer (CRPC)1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMetastatic Bladder Cancer / Urinary Tract Neoplasms / Urologic Neoplasms1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
ClassificationNot classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin binding
Specific Function:
Involved in stress resistance and actin organization.
Gene Name:
HSPB1
Uniprot ID:
P04792
Molecular Weight:
22782.3 Da
Drug created on November 18, 2007 11:29 / Updated on June 22, 2017 10:01