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{{Short description|Chemical compound}}
{{drugbox
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
⚫ | verifiedrevid = 444399735
⚫ | IUPAC_name =
| image = Oblimersen.svg
| width = 300

<!--Clinical data-->
| tradename = Genasense
⚫ | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫ | pregnancy_US = <!-- A / B / C / D / X -->
⚫ | pregnancy_category =
⚫ | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
⚫ | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫ | legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫ | legal_status = Not marketed
⚫ | routes_of_administration =

<!--Pharmacokinetic data-->
⚫ | bioavailability =
⚫ | protein_bound =
⚫ | metabolism =
⚫ | elimination_half-life =
⚫ | excretion =

<!--Identifiers-->
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 34980574
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 190977-41-4
⚫ | ATC_prefix = L01
⚫ | ATC_suffix = XX36
| PubChem = Oblimersen
⚫ | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
⚫ | DrugBank =
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 85J5ZP6YSL | UNII = 85J5ZP6YSL
| synonyms = G3139
⚫ | verifiedrevid = 442311100

⚫ | IUPAC_name =
<!--Chemical data-->
| image =
| CAS_number = | C=172 | H=221 | N=62 | O=91 | P=17 | S=17
⚫ | molecular_weight =
⚫ | ATC_prefix = L01
| smiles = Cc1cn(c(=O)c1=O)2C((O2)COP(=O)(O3C(O3COP(=O)(O4C(O4COP(=O)(O5C(O5COP(=O)(O6C(O6COP(=O)(O7C(O7COP(=O)(O8C(O8COP(=O)(O9C(O9COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1CO)n1cc(c(=O)c1=O)C)S)n1ccc(nc1=O)N)S)n1cc(c(=O)c1=O)C)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc(c2=O)N)S)n1cc(c(=O)c1=O)C)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)O
⚫ | ATC_suffix = XX36
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| PubChem =
| StdInChI = 1S/C172H221N62O91P17S17/c1-69-39-225(169(253)213-149(69)237)117-21-73(236)92(292-117)44-274-326(257,343)320-85-33-129(229-63-191-135-141(181)187-61-189-143(135)229)303-103(85)55-285-332(263,349)314-79-27-122(221-17-9-113(177)201-165(221)249)295-95(79)47-278-330(261,347)312-78-26-121(220-16-8-112(176)200-164(220)248)298-98(78)50-280-338(269,355)322-87-35-131(231-65-193-137-145(231)205-157(183)209-153(137)241)305-105(87)57-287-334(265,351)316-81-29-124(223-19-11-115(179)203-167(223)251)299-99(81)51-281-339(270,356)323-88-36-132(232-66-194-138-146(232)206-158(184)210-154(138)242)307-107(88)59-289-337(268,354)319-84-32-128(228-42-72(4)152(240)216-172(228)256)302-102(84)54-284-341(272,358)325-90-38-134(234-68-196-140-148(234)208-160(186)212-156(140)244)306-106(90)58-288-335(266,352)317-82-30-125(224-20-12-116(180)204-168(224)252)300-100(82)52-282-340(271,357)324-89-37-133(233-67-195-139-147(233)207-159(185)211-155(139)243)308-108(89)60-290-342(273,359)321-86-34-130(230-64-192-136-142(182)188-62-190-144(136)230)304-104(86)56-286-333(264,350)315-80-28-123(222-18-10-114(178)202-166(222)250)296-96(80)48-277-328(259,345)310-76-24-119(218-14-6-110(174)198-162(218)246)294-94(76)46-276-329(260,346)311-77-25-120(219-15-7-111(175)199-163(219)247)297-97(77)49-279-336(267,353)318-83-31-127(227-41-71(3)151(239)215-171(227)255)301-101(83)53-283-331(262,348)313-75-23-118(217-13-5-109(173)197-161(217)245)293-93(75)45-275-327(258,344)309-74-22-126(291-91(74)43-235)226-40-70(2)150(238)214-170(226)254/h5-20,39-42,61-68,73-108,117-134,235-236H,21-38,43-60H2,1-4H3,(H,257,343)(H,258,344)(H,259,345)(H,260,346)(H,261,347)(H,262,348)(H,263,349)(H,264,350)(H,265,351)(H,266,352)(H,267,353)(H,268,354)(H,269,355)(H,270,356)(H,271,357)(H,272,358)(H,273,359)(H2,173,197,245)(H2,174,198,246)(H2,175,199,247)(H2,176,200,248)(H2,177,201,249)(H2,178,202,250)(H2,179,203,251)(H2,180,204,252)(H2,181,187,189)(H2,182,188,190)(H,213,237,253)(H,214,238,254)(H,215,239,255)(H,216,240,256)(H3,183,205,209,241)(H3,184,206,210,242)(H3,185,207,211,243)(H3,186,208,212,244)/t73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91+,92+,93+,94+,95+,96+,97+,98+,99+,100+,101+,102+,103+,104+,105+,106+,107+,108+,117+,118+,119+,120+,121+,122+,123+,124+,125+,126+,127+,128+,129+,130+,131+,132+,133+,134+,326?,327?,328?,329?,330?,331?,332?,333?,334?,335?,336?,337?,338?,339?,340?,341?,342?/m0/s1
⚫ | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
⚫ | DrugBank =
| StdInChIKey = MIMNFCVQODTQDP-NDLVEFNKSA-N
| chemical_formula =
⚫ | molecular_weight =
⚫ | bioavailability =
⚫ | protein_bound =
⚫ | metabolism =
⚫ | elimination_half-life =
⚫ | excretion =
⚫ | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫ | pregnancy_US = <!-- A / B / C / D / X -->
⚫ | pregnancy_category=
⚫ | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
⚫ | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫ | legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫ | legal_status =
⚫ | routes_of_administration =
}} }}

'''Oblimersen''' (], trade name '''Genasense'''; also known as '''Augmerosen''' and '''bcl-2 antisense oligodeoxynucleotide G3139''') is an ] ] being studied as a possible treatment for several types of ], including ], ], and ]. It may kill cancer cells by blocking the production of ]—a ] that makes cancer cells live longer—and by making them more sensitive to chemotherapy. '''Oblimersen''' (], trade name '''Genasense'''; also known as '''Augmerosen''' and '''bcl-2 antisense oligodeoxynucleotide G3139''') is an ] ] being studied as a possible treatment for several types of ], including ], ], and ]. It may kill cancer cells by blocking the production of ]—a ] that makes cancer cells live longer—and by making them more sensitive to chemotherapy.


==History== ==History==
An antisense ] drug ] (G3139) has been developed by ] to target Bcl-2. An ] DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An ] is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed. The antisense ] drug oblimersen was developed by ] to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.{{cn|date=February 2023}}


It was shown that the proliferation of human ] ] (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start ] region of Bcl-2 ]. ] studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.<ref name="pmid12445555">{{cite journal | author = Dias N, Stein CA | title = Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides | journal = Eur J Pharm Biopharm | volume = 54 | issue = 3 | pages = 263–9 | year = 2002 | month = November | pmid = 12445555 | doi = 10.1016/S0939-6411(02)00060-7| url = http://linkinghub.elsevier.com/retrieve/pii/S0939641102000607 }}</ref> It was shown that the proliferation of human ] ] (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start ] region of Bcl-2 ]. ] studies led to the identification of oblimersen, which is complementary to the first 6 codons of Bcl-2 mRNA.<ref name="pmid12445555">{{cite journal | vauthors = Dias N, Stein CA | title = Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides | journal = European Journal of Pharmaceutics and Biopharmaceutics | volume = 54 | issue = 3 | pages = 263–9 | date = November 2002 | pmid = 12445555 | doi = 10.1016/S0939-6411(02)00060-7 }}</ref>


These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004<ref name="pmid15010151">{{cite journal | author = Mavromatis BH, Cheson BD | title = Novel therapies for chronic lymphocytic leukemia | journal = Blood Rev. | volume = 18 | issue = 2 | pages = 137–48 | year = 2004 | month = June | pmid = 15010151 | doi = 10.1016/S0268-960X(03)00039-0 | url = }}</ref> These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004.<ref name="pmid15010151">{{cite journal | vauthors = Mavromatis BH, Cheson BD | title = Novel therapies for chronic lymphocytic leukemia | journal = Blood Reviews | volume = 18 | issue = 2 | pages = 137–48 | date = June 2004 | pmid = 15010151 | doi = 10.1016/S0268-960X(03)00039-0 }}</ref>


By the first quarter 2010, Genasense had not received ] approval due to disappointing results in a melanoma trial. Although safety and efficacy of Genasense have not been established for any use, Genta Incorporated still claims on its website that studies are currently underway to examine the potential role of Genasense in a variety of clinical indications. By the first quarter 2010, the drug had not received ] approval due to disappointing results in a melanoma trial. Although its safety and efficacy have not been established for any use, Genta Incorporated still{{When|date=August 2021}} claims on its website that studies are currently under way to examine the potential role of oblimersen in a variety of clinical indications.


Recent studies in 2023 continue to explore the potential of oblimersen in combination with other therapies. Preclinical models have demonstrated that oblimersen, when combined with vinorelbine, significantly inhibits tumor growth and prolongs survival in NSCLC. These findings suggest that combining oblimersen with other chemotherapeutic agents could enhance its efficacy and potentially overcome previous clinical challenges.
⚫ ==References==

⚫ == References ==
{{reflist}} {{reflist}}


== External links == == External links ==
* entry in the public domain NCI Dictionary of Cancer Terms * entry in the public domain NCI Dictionary of Cancer Terms


{{Chemotherapeutic agents}} {{Chemotherapeutic agents}}



] ]
]

]

{{antineoplastic-drug-stub}}

Latest revision as of 11:47, 22 June 2024

Chemical compound Pharmaceutical compound
Oblimersen
Clinical data
Trade namesGenasense
Other namesG3139
ATC code
Legal status
Legal status
  • Not marketed
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC172H221N62O91P17S17
Molar mass5684.58 g·mol
3D model (JSmol)
SMILES
  • Cc1cn(c(=O)c1=O)2C((O2)COP(=O)(O3C(O3COP(=O)(O4C(O4COP(=O)(O5C(O5COP(=O)(O6C(O6COP(=O)(O7C(O7COP(=O)(O8C(O8COP(=O)(O9C(O9COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1COP(=O)(O1C(O1CO)n1cc(c(=O)c1=O)C)S)n1ccc(nc1=O)N)S)n1cc(c(=O)c1=O)C)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc(c2=O)N)S)n1cc(c(=O)c1=O)C)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1nc(c2=O)N)S)n1ccc(nc1=O)N)S)n1ccc(nc1=O)N)S)n1cnc2c1ncnc2N)S)O
InChI
  • InChI=1S/C172H221N62O91P17S17/c1-69-39-225(169(253)213-149(69)237)117-21-73(236)92(292-117)44-274-326(257,343)320-85-33-129(229-63-191-135-141(181)187-61-189-143(135)229)303-103(85)55-285-332(263,349)314-79-27-122(221-17-9-113(177)201-165(221)249)295-95(79)47-278-330(261,347)312-78-26-121(220-16-8-112(176)200-164(220)248)298-98(78)50-280-338(269,355)322-87-35-131(231-65-193-137-145(231)205-157(183)209-153(137)241)305-105(87)57-287-334(265,351)316-81-29-124(223-19-11-115(179)203-167(223)251)299-99(81)51-281-339(270,356)323-88-36-132(232-66-194-138-146(232)206-158(184)210-154(138)242)307-107(88)59-289-337(268,354)319-84-32-128(228-42-72(4)152(240)216-172(228)256)302-102(84)54-284-341(272,358)325-90-38-134(234-68-196-140-148(234)208-160(186)212-156(140)244)306-106(90)58-288-335(266,352)317-82-30-125(224-20-12-116(180)204-168(224)252)300-100(82)52-282-340(271,357)324-89-37-133(233-67-195-139-147(233)207-159(185)211-155(139)243)308-108(89)60-290-342(273,359)321-86-34-130(230-64-192-136-142(182)188-62-190-144(136)230)304-104(86)56-286-333(264,350)315-80-28-123(222-18-10-114(178)202-166(222)250)296-96(80)48-277-328(259,345)310-76-24-119(218-14-6-110(174)198-162(218)246)294-94(76)46-276-329(260,346)311-77-25-120(219-15-7-111(175)199-163(219)247)297-97(77)49-279-336(267,353)318-83-31-127(227-41-71(3)151(239)215-171(227)255)301-101(83)53-283-331(262,348)313-75-23-118(217-13-5-109(173)197-161(217)245)293-93(75)45-275-327(258,344)309-74-22-126(291-91(74)43-235)226-40-70(2)150(238)214-170(226)254/h5-20,39-42,61-68,73-108,117-134,235-236H,21-38,43-60H2,1-4H3,(H,257,343)(H,258,344)(H,259,345)(H,260,346)(H,261,347)(H,262,348)(H,263,349)(H,264,350)(H,265,351)(H,266,352)(H,267,353)(H,268,354)(H,269,355)(H,270,356)(H,271,357)(H,272,358)(H,273,359)(H2,173,197,245)(H2,174,198,246)(H2,175,199,247)(H2,176,200,248)(H2,177,201,249)(H2,178,202,250)(H2,179,203,251)(H2,180,204,252)(H2,181,187,189)(H2,182,188,190)(H,213,237,253)(H,214,238,254)(H,215,239,255)(H,216,240,256)(H3,183,205,209,241)(H3,184,206,210,242)(H3,185,207,211,243)(H3,186,208,212,244)/t73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91+,92+,93+,94+,95+,96+,97+,98+,99+,100+,101+,102+,103+,104+,105+,106+,107+,108+,117+,118+,119+,120+,121+,122+,123+,124+,125+,126+,127+,128+,129+,130+,131+,132+,133+,134+,326?,327?,328?,329?,330?,331?,332?,333?,334?,335?,336?,337?,338?,339?,340?,341?,342?/m0/s1
  • Key:MIMNFCVQODTQDP-NDLVEFNKSA-N
  (what is this?)  (verify)

Oblimersen (INN, trade name Genasense; also known as Augmerosen and bcl-2 antisense oligodeoxynucleotide G3139) is an antisense oligodeoxyribonucleotide being studied as a possible treatment for several types of cancer, including chronic lymphocytic leukemia, B-cell lymphoma, and breast cancer. It may kill cancer cells by blocking the production of Bcl-2—a protein that makes cancer cells live longer—and by making them more sensitive to chemotherapy.

History

The antisense oligonucleotide drug oblimersen was developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.

It was shown that the proliferation of human lymphoma cells (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of oblimersen, which is complementary to the first 6 codons of Bcl-2 mRNA.

These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004.

By the first quarter 2010, the drug had not received FDA approval due to disappointing results in a melanoma trial. Although its safety and efficacy have not been established for any use, Genta Incorporated still claims on its website that studies are currently under way to examine the potential role of oblimersen in a variety of clinical indications.

Recent studies in 2023 continue to explore the potential of oblimersen in combination with other therapies. Preclinical models have demonstrated that oblimersen, when combined with vinorelbine, significantly inhibits tumor growth and prolongs survival in NSCLC. These findings suggest that combining oblimersen with other chemotherapeutic agents could enhance its efficacy and potentially overcome previous clinical challenges.

References

  1. Dias N, Stein CA (November 2002). "Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". European Journal of Pharmaceutics and Biopharmaceutics. 54 (3): 263–9. doi:10.1016/S0939-6411(02)00060-7. PMID 12445555.
  2. Mavromatis BH, Cheson BD (June 2004). "Novel therapies for chronic lymphocytic leukemia". Blood Reviews. 18 (2): 137–48. doi:10.1016/S0268-960X(03)00039-0. PMID 15010151.

External links

  • Augmerosen entry in the public domain NCI Dictionary of Cancer Terms
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