AGRO100

Identification

Generic Name
AGRO100
DrugBank Accession Number
DB04998
Background

AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Pre-clinical testing demonstrates that the AGRO100 inhibition of nucleolin function produces anti-cancer effects against multiple types of the disease, including lung, prostate, breast, cervical, and colon cancer, as well as malignant melanoma and leukemia.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 8272.338
Monoisotopic: 8268.35141579
Chemical Formula
C260H322N103O163P25
Synonyms
Not Available
External IDs
  • AGRO-100
  • AGRO100
  • AS 1411
  • AS-1411
  • AS1411

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified), kidney cancer, leukemia (myeloid), and pancreatic cancer.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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Avoid life-threatening adverse drug events & improve clinical decision support.
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Pharmacodynamics

Not Available

Mechanism of action

AGRO100, an experimental anticancer drug that recently entered human clinical trials, is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides (GRO), which are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins as aptamers. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells. AGRO100 also associates with nuclear factor-{kappa}B (NF-{kappa}B) essential modulator (NEMO), which is a regulatory subunit of the inhibitor of {kappa}B (I{kappa}B) kinase (IKK) complex, and also called IKK{gamma}. In the classic NF-{kappa}B pathway, the IKK complex is required for phosphorylation of I{kappa}B{alpha} and subsequent activation of the transcription factor NF-{kappa}B. Research shows that treatment of cancer cells with AGRO100 inhibits IKK activity and reduces phosphorylation of I{kappa}B{alpha} in response to tumor necrosis factor-{alpha} stimulation. It also shows that AGRO100 blocks both tumor necrosis factor-{alpha}-induced and constitutive NF-{kappa}B activity in human cancer cell lines derived from cervical, prostate, breast, and lung carcinomas. In addition, in AGRO100-treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both proteins are present in the same complex. Studies suggest that abrogation of NF-{kappa}B activity may contribute to the anticancer effects of AGRO100 and that nucleolin may play a previously unknown role in regulating the NF-{kappa}B pathway. [PubMed: 16891465]

TargetActionsOrganism
UNF-kappa-B essential modulatorNot AvailableHumans
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
Adverseeffects
Improve decision support & research outcomes
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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
Z03K553649
CAS number
301636-59-9
InChI Key
DFYPFJSPLUVPFJ-QJEDTDQSSA-N
InChI
InChI=1S/C260H322N103O163P25/c1-88-36-338(252(392)329-209(88)366)150-12-99(126(479-150)48-455-540(427,428)515-111-24-163(352-76-283-180-197(352)300-240(266)317-223(180)380)496-143(111)65-470-546(439,440)521-118-31-170(359-83-290-187-204(359)307-247(273)324-230(187)387)492-139(118)61-466-534(415,416)508-104-17-155(343-41-93(6)214(371)334-257(343)397)483-130(104)52-459-544(435,436)519-115-28-167(356-80-287-184-201(356)304-244(270)321-227(184)384)500-147(115)69-474-550(447,448)525-121-34-173(362-86-293-190-207(362)310-250(276)327-233(190)390)494-141(121)63-468-536(419,420)510-106-19-157(345-43-95(8)216(373)336-259(345)399)484-131(106)53-458-542(431,432)517-113-26-165(354-78-285-182-199(354)302-242(268)319-225(182)382)498-145(113)67-472-548(443,444)522-117-30-169(358-82-289-186-203(358)306-246(272)323-229(186)386)490-137(117)59-464-532(411,412)506-102-15-153(341-39-91(4)212(369)332-255(341)395)480-127(102)49-454-538(423,424)513-109-22-161(350-74-281-178-195(350)298-238(264)315-221(178)378)487-134(109)56-452-528(403,404)502-98-11-159(476-123(98)45-364)348-72-279-176-193(348)296-236(262)313-219(176)376)503-529(405,406)453-47-125-100(13-151(478-125)339-37-89(2)210(367)330-253(339)393)504-531(409,410)463-58-136-110(23-162(489-136)351-75-282-179-196(351)299-239(265)316-222(179)379)514-539(425,426)456-51-129-103(16-154(482-129)342-40-92(5)213(370)333-256(342)396)507-533(413,414)465-60-138-119(32-171(491-138)360-84-291-188-205(360)308-248(274)325-231(188)388)523-549(445,446)473-68-146-114(27-166(499-146)355-79-286-183-200(355)303-243(269)320-226(183)383)518-543(433,434)460-55-133-107(20-158(486-133)346-44-96(9)217(374)337-260(346)400)511-537(421,422)469-64-142-122(35-174(495-142)363-87-294-191-208(363)311-251(277)328-234(191)391)526-551(449,450)475-70-148-116(29-168(501-148)357-81-288-185-202(357)305-245(271)322-228(185)385)520-545(437,438)461-54-132-105(18-156(485-132)344-42-94(7)215(372)335-258(344)398)509-535(417,418)467-62-140-120(33-172(493-140)361-85-292-189-206(361)309-249(275)326-232(189)389)524-547(441,442)471-66-144-112(25-164(497-144)353-77-284-181-198(353)301-241(267)318-224(181)381)516-541(429,430)457-50-128-101(14-152(481-128)340-38-90(3)211(368)331-254(340)394)505-530(407,408)462-57-135-108(21-160(488-135)349-73-280-177-194(349)297-237(263)314-220(177)377)512-527(401,402)451-46-124-97(365)10-149(477-124)347-71-278-175-192(347)295-235(261)312-218(175)375/h36-44,71-87,97-174,364-365H,10-35,45-70H2,1-9H3,(H,401,402)(H,403,404)(H,405,406)(H,407,408)(H,409,410)(H,411,412)(H,413,414)(H,415,416)(H,417,418)(H,419,420)(H,421,422)(H,423,424)(H,425,426)(H,427,428)(H,429,430)(H,431,432)(H,433,434)(H,435,436)(H,437,438)(H,439,440)(H,441,442)(H,443,444)(H,445,446)(H,447,448)(H,449,450)(H,329,366,392)(H,330,367,393)(H,331,368,394)(H,332,369,395)(H,333,370,396)(H,334,371,397)(H,335,372,398)(H,336,373,399)(H,337,374,400)(H3,261,295,312,375)(H3,262,296,313,376)(H3,263,297,314,377)(H3,264,298,315,378)(H3,265,299,316,379)(H3,266,300,317,380)(H3,267,301,318,381)(H3,268,302,319,382)(H3,269,303,320,383)(H3,270,304,321,384)(H3,271,305,322,385)(H3,272,306,323,386)(H3,273,307,324,387)(H3,274,308,325,388)(H3,275,309,326,389)(H3,276,310,327,390)(H3,277,311,328,391)/t97-,98?,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123?,124+,125+,126+,127+,128+,129+,130+,131+,132+,133+,134+,135+,136+,137+,138+,139+,140+,141+,142+,143+,144+,145+,146+,147+,148+,149+,150+,151+,152+,153+,154+,155+,156+,157+,158+,159?,160+,161+,162+,163+,164+,165+,166+,167+,168+,169+,170+,171+,172+,173+,174+/m0/s1
IUPAC Name
{[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[(2R,3S,5R)-2-({[hydroxy({[5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-3-yl]oxy})phosphoryl]oxy}methyl)-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-3-yl]oxy}({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-{[hydroxy({[(2R,3S,5R)-3-hydroxy-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(6-hydroxy-2-imino-3,9-dihydro-2H-purin-9-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}-5-(4-hydroxy-5-methyl-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphinic acid
SMILES
[H][C@]1(O)C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)O[C@@]1([H])C[C@@]([H])(O[C@]1([H])COP(O)(=O)OC1([H])CC([H])(OC1([H])CO)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O)N1C=C(C)C(O)=NC1=O)N1C=NC2=C1NC(=N)N=C2O)N1C=NC2=C1NC(=N)N=C2O

References

General References
Not Available
PubChem Substance
347909883

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentMyeloid Leukemias1
2TerminatedTreatmentAcute Myeloid Leukemia (AML)1
2Unknown StatusTreatmentMetastatic Renal Cell Carcinoma ( mRCC)1
1CompletedTreatmentSolid Tumors, Advanced Solid Tumors1

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
logP-6.3ChemAxon
pKa (Strongest Acidic)0.95ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count190ChemAxon
Hydrogen Donor Count87ChemAxon
Polar Surface Area3617.47 Å2ChemAxon
Rotatable Bond Count152ChemAxon
Refractivity1931.71 m3·mol-1ChemAxon
Polarizability735.41 Å3ChemAxon
Number of Rings69ChemAxon
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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the i...
Gene Name
IKBKG
Uniprot ID
Q9Y6K9
Uniprot Name
NF-kappa-B essential modulator
Molecular Weight
48197.35 Da

Drug created on October 21, 2007 22:23 / Updated on June 12, 2020 16:52