Apatorsen

Identification

Name
Apatorsen
Accession Number
DB06094
Type
Small Molecule
Groups
Investigational
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
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Apatorsen sodium3N4G7RE66Y915443-09-3Not applicable
Categories
UNII
IFJ6X26JW6
CAS number
1002331-21-6
Weight
Average: 7156.97
Monoisotopic: 7152.002582293
Chemical Formula
C224H304N79O116P19S19
InChI Key
RMTMMKNSPRRFHW-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
({2-[({[(2-{[({[2-({[({2-[({[(2-{[({[2-({[({2-[({[(2-{[({[5-(6-amino-9H-purin-9-yl)-2-({[hydroxy({[2-({[hydroxy({[2-({[hydroxy({[5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy})sulfanylidene-lambda5-phosphanyl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy})sulfanylidene-lambda5-phosphanyl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy})sulfanylidene-lambda5-phosphanyl]oxy}methyl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy}(hydroxy)sulfanylidene-lambda5-phosphanyl)oxy]methyl}-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)oxolan-3-yl)oxy](hydroxy)sulfanylidene-lambda5-phosphanyl}oxy)methyl]-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl}oxy)(hydroxy)sulfanylidene-lambda5-phosphanyl]oxy}methyl)-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)oxolan-3-yl]oxy}(hydroxy)sulfanylidene-lambda5-phosphanyl)oxy]methyl}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl)oxy](hydroxy)sulfanylidene-lambda5-phosphanyl}oxy)methyl]-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl}oxy)(hydroxy)sulfanylidene-lambda5-phosphanyl]oxy}methyl)-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)oxolan-3-yl]oxy}(hydroxy)sulfanylidene-lambda5-phosphanyl)oxy]methyl}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl)oxy](hydroxy)sulfanylidene-lambda5-phosphanyl}oxy)methyl]-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)oxolan-3-yl}oxy)({[3-({[(3-{[({3-[({[3-({[(3-{[({3-[({[5-(6-amino-9H-purin-9-yl)-3-{[hydroxy({[3-hydroxy-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-4-(2-methoxyethoxy)oxolan-2-yl]methoxy})sulfanylidene-lambda5-phosphanyl]oxy}-4-(2-methoxyethoxy)oxolan-2-yl]methoxy}(hydroxy)sulfanylidene-lambda5-phosphanyl)oxy]-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)-4-(2-methoxyethoxy)oxolan-2-yl}methoxy)(hydroxy)sulfanylidene-lambda5-phosphanyl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)-4-(2-methoxyethoxy)oxolan-2-yl)methoxy](hydroxy)sulfanylidene-lambda5-phosphanyl}oxy)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy}(hydroxy)sulfanylidene-lambda5-phosphanyl)oxy]-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl}methoxy)(hydroxy)sulfanylidene-lambda5-phosphanyl]oxy}-5-(2-hydroxy-4-imino-5-methyl-1,4-dihydropyrimidin-1-yl)oxolan-2-yl)methoxy](hydroxy)sulfanylidene-lambda5-phosphanyl}oxy)-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})sulfanylidenephosphinous acid
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
TargetActionsOrganism
UHeat shock protein beta-1Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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 Links
PubChem Compound
131704298
PubChem Substance
347827755

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeoplasms1
1Unknown StatusTreatmentBladder Cancers1
2Active Not RecruitingTreatmentNon Squamous Non Small Cell Lung Cancer1
2Active Not RecruitingTreatmentSquamous Cell Carcinoma of Lung1
2CompletedTreatmentBladder Cancers / Transitional Cell Carcinoma1
2CompletedTreatmentCastration Resistant Prostate Cancer (CRPC)1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMetastatic Bladder Cancer / Urinary Tract Neoplasms / Urologic Neoplasms1
2TerminatedTreatmentMetastatic Castrate-Resistant Prostate Cancer / Prostate Cancer / PsA1

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
PropertyValueSource
logP11.4ChemAxon
pKa (Strongest Acidic)1.01ChemAxon
Physiological Charge-7ChemAxon
Hydrogen Acceptor Count143ChemAxon
Hydrogen Donor Count65ChemAxon
Polar Surface Area2540.48 Å2ChemAxon
Rotatable Bond Count148ChemAxon
Refractivity1791.67 m3·mol-1ChemAxon
Polarizability662.51 Å3ChemAxon
Number of Rings51ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not 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
Uniprot Name
Heat shock protein beta-1
Molecular Weight
22782.3 Da

Drug created on November 18, 2007 11:29 / Updated on December 01, 2017 15:37