Identification

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Name
AGRO100
Accession Number
DB04998
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
AGRO-100 / AGRO100 / AS 1411 / AS-1411 / AS1411
Categories
UNII
Z03K553649
CAS number
301636-59-9
Weight
Average: 8272.338
Monoisotopic: 8268.35141579
Chemical Formula
C260H322N103O163P25
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
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

Pharmacology

Indication

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

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
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
Not Available
External Links
PubChem Substance
347909883

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Solid Tumors1
2CompletedTreatmentMyeloid Leukemias1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Unknown StatusTreatmentMetastatic Renal Cell Carcinoma1

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
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

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 16:23 / Updated on June 04, 2019 06:14