Donidalorsen

Last updated

Donidalorsen
Donidalorsen.svg
Clinical data
Trade names Dawnzera
Other namesISIS 721744, ISIS-721744
AHFS/Drugs.com Dawnzera
License data
Routes of
administration 		Subcutaneous
ATC code
  • None
Legal status
Legal status
Identifiers
  • all-P-ambo-5'-O-(((6-(5-((tris(3-(6-(2-acetamido-2-deoxy-β-D-galactopyranosyloxy)hexylamino)-3-oxopropoxymethyl))methyl)amino-5-oxopentanamido)hexyl))phospho)-2'-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methylcytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)adenylyl-(3'→5')-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2-methoxyethyl)adenosine
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C296H435N83O151P20S15
Molar mass 8672.54 g·mol−1
  • COCCO[C@@H]1[C@H](OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(=O)[nH]c(N)nc43)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)C[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(=O)(O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cc(C)c(N)nc3=O)[C@H](OCCOC)[C@@H]2OP(O)(=S)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc43)[C@H](OCCOC)[C@@H]2O)[C@@H](COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cnc4c(=O)[nH]c(N)nc43)O[C@@H]2COP(O)(=S)O[C@H]2[C@@H](OCCOC)[C@H](n3cc(C)c(=O)[nH]c3=O)O[C@@H]2COP(=O)(O)OCCCCCCNC(=O)CCCC(=O)NC(COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)(COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)COCCC(=O)NCCCCCCO[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2NC(C)=O)O[C@H]1n1cc(C)c(N)nc1=O
  • InChI=1S/C296H435N83O151P20S15/c1-139-87-360(286(407)341-239(139)297)190-77-152(513-537(428,552)477-104-169-156(81-194(493-169)364-93-145(7)261(399)355-292(364)413)516-540(431,555)478-105-170-158(83-196(494-170)366-95-147(9)263(401)357-294(366)415)517-541(432,556)481-107-172-160(85-198(496-172)371-130-335-210-257(371)347-283(309)351-266(210)404)520-544(435,559)482-108-173-159(84-197(497-173)370-129-334-209-256(370)346-282(308)350-265(209)403)519-542(433,557)479-102-167-154(79-192(491-167)362-89-141(3)241(299)343-288(362)409)518-545(436,560)485-116-182-223(233(459-71-61-446-18)275(507-182)376-135-331-206-247(305)319-126-325-253(206)376)525-533(421,422)471-113-177-221(232(458-70-60-445-17)274(504-177)375-134-330-205-246(304)318-125-324-252(205)375)523-535(425,426)473-115-180-226(237(463-75-65-450-22)277(506-180)378-137-333-208-249(307)321-128-327-255(208)378)528-550(441,565)487-118-183-227(235(461-73-63-448-20)271(502-183)368-91-143(5)243(301)345-290(368)411)529-547(438,562)484-110-175-216(394)229(455-67-57-442-14)269(499-175)373-132-328-203-244(302)316-123-322-250(203)373)165(489-190)100-474-538(429,553)514-155-80-193(363-92-144(6)260(398)354-291(363)412)492-168(155)103-476-536(427,551)512-153-78-191(361-88-140(2)240(298)342-287(361)408)490-166(153)101-475-539(430,554)515-157-82-195(365-94-146(8)262(400)356-293(365)414)495-171(157)106-480-543(434,558)521-161-86-199(372-131-336-211-258(372)348-284(310)352-267(211)405)498-174(161)109-483-546(437,561)527-225-179(505-276(236(225)462-74-64-449-21)377-136-332-207-248(306)320-127-326-254(207)377)114-472-534(423,424)522-220-176(503-273(231(220)457-69-59-444-16)374-133-329-204-245(303)317-124-323-251(204)374)112-470-532(419,420)524-222-181(501-270(230(222)456-68-58-443-15)367-90-142(4)242(300)344-289(367)410)117-486-548(439,563)530-228-184(508-278(238(228)464-76-66-451-23)379-138-337-212-259(379)349-285(311)353-268(212)406)119-488-549(440,564)526-224-178(500-272(234(224)460-72-62-447-19)369-96-148(10)264(402)358-295(369)416)111-469-531(417,418)468-53-39-31-27-35-46-312-185(386)41-40-42-189(390)359-296(120-452-54-43-186(387)313-47-32-24-28-36-50-465-279-200(338-149(11)383)217(395)213(391)162(97-380)509-279,121-453-55-44-187(388)314-48-33-25-29-37-51-466-280-201(339-150(12)384)218(396)214(392)163(98-381)510-280)122-454-56-45-188(389)315-49-34-26-30-38-52-467-281-202(340-151(13)385)219(397)215(393)164(99-382)511-281/h87-96,123-138,152-184,190-202,213-238,269-281,380-382,391-397H,24-86,97-122H2,1-23H3,(H,312,386)(H,313,387)(H,314,388)(H,315,389)(H,338,383)(H,339,384)(H,340,385)(H,359,390)(H,417,418)(H,419,420)(H,421,422)(H,423,424)(H,425,426)(H,427,551)(H,428,552)(H,429,553)(H,430,554)(H,431,555)(H,432,556)(H,433,557)(H,434,558)(H,435,559)(H,436,560)(H,437,561)(H,438,562)(H,439,563)(H,440,564)(H,441,565)(H2,297,341,407)(H2,298,342,408)(H2,299,343,409)(H2,300,344,410)(H2,301,345,411)(H2,302,316,322)(H2,303,317,323)(H2,304,318,324)(H2,305,319,325)(H2,306,320,326)(H2,307,321,327)(H,354,398,412)(H,355,399,413)(H,356,400,414)(H,357,401,415)(H,358,402,416)(H3,308,346,350,403)(H3,309,347,351,404)(H3,310,348,352,405)(H3,311,349,353,406)/t152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162+,163+,164+,165+,166+,167+,168+,169+,170+,171+,172+,173+,174+,175+,176+,177+,178+,179+,180+,181+,182+,183+,184+,190+,191+,192+,193+,194+,195+,196+,197+,198+,199+,200+,201+,202+,213-,214-,215-,216+,217+,218+,219+,220+,221+,222+,223+,224+,225+,226+,227+,228+,229+,230+,231+,232+,233+,234+,235+,236+,237+,238+,269+,270+,271+,272+,273+,274+,275+,276+,277+,278+,279+,280+,281+,536?,537?,538?,539?,540?,541?,542?,543?,544?,545?,546?,547?,548?,549?,550?/m0/s1
  • Key:OHKXUCDSZDEIHM-ADAMUUMMSA-N

Donidalorsen, sold under the brand name Dawnzera, is a medication used to prevent attacks of hereditary angioedema. [1] Donidalorsen is a prekallikrein-directed antisense oligonucleotide. [1] It is given by injection under the skin (subcutaneous). [1]

Contents

Donidalorsen was approved for medical use in the United States in August 2025. [2]

Medical uses

Donidalorsen is indicated for prophylaxis to prevent attacks of hereditary angioedema. [1]

Mechanism of action

Donidalorsen is an antisense oligonucleotide designed to treat hereditary angioedema (HAE) by targeting and reducing the production of prekallikrein (PKK), a key protein involved in triggering inflammatory mediators responsible for HAE attacks. It works by binding to the messenger RNA (mRNA) of the KLKB1 gene, which encodes prekallikrein, and promoting the breakdown of this mRNA. As a result, the synthesis of PKK protein is decreased. Lower PKK levels reduce the downstream production of bradykinin, a potent vasodilator implicated in the swelling episodes characteristic of HAE. Through this RNA-targeted mechanism, donidalorsen lowers the frequency and severity of angioedema attacks by interrupting the pathway responsible for excessive bradykinin generation. [3] [4]

Society and culture

Donidalorsen was approved for medical use in the United States in August 2025. [5]

Names

Donidalorsen is the international nonproprietary name. [6]

Donidalorsen is sold under the brand name Dawnzera. [1]

References

  1. 1 2 3 4 5 6 "DAWNZERA (donidalorsen) injection, for subcutaneous use" (PDF). Highlights of Prescribing Information. Ionis Pharmaceuticals, Inc.
  2. ↑ "Dawnzera (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema" (Press release). Ionis Pharmaceuticals, Inc. 21 August 2025. Retrieved 22 August 2025– via Business Wire.
  3. ↑ "Donidalorsen: An Investigational RNA-targeted Medicine" (PDF). Ionis Pharmaceuticals, Inc.
  4. ↑ Farkas H, Balla Z (March 2024). "Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies". Expert Opinion on Investigational Drugs. 33 (3): 191–200. doi:10.1080/13543784.2024.2320700. PMID   38366937.
  5. ↑ "Dawnzera: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 22 August 2025.
  6. ↑ World Health Organization (2021). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 86". WHO Drug Information. 35 (3). hdl: 10665/346562 .

Further reading


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.