Miscellaneous & Research; Cognitive & Neuroprotection

PACAP (Pituitary Adenylate Cyclase-Activating Peptide)

Infuse PACAP — pituitary adenylate cyclase-activating peptide — into someone prone to migraine and an attack follows. In randomised, placebo-controlled crossover trials, PACAP-38 provoked migraine-like attacks in 7 of 12 patients and none on placebo, and the shorter PACAP-27 in 11 of 20 against 2 on placebo. That reliability is what makes it one of the more credible targets in headache research, and why the drug development here runs backwards from the rest of this corpus: the aim is to block PACAP, not to supply it. A Phase 2 trial of an antibody against the peptide is on file, and there is no use of PACAP itself as a treatment.

Last updated 12 August 2026

Studied forMigraine mechanism research · Antibody target research · Neuroprotection research

Evidence on file1 randomised human trial · 2 animal studies · 1 citation not yet graded

Strongest sourceNCT05133323: Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Lu AG09222… (randomised human trial)

Mechanism

Activates PAC1, VPAC1, and VPAC2 receptors, raising cyclic AMP, dilating dural vessels, and exciting trigeminovascular nociception.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Migraine mechanism research
Antibody target research
Neuroprotection research

Dosing on file unverified

PACAP-38: migraine induction studies; Monoclonal antibodies: Phase 2 (LY3451838 1,500 mg IV, Lu AG09222); Monoclonal antibodies: LY3451838 1,500 mg IV single dose (Phase 2); Lu AG09222 Phase 2

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

Literature on file 4

human RCT
NCT05133323: Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Lu AG09222 for the Prevention of Migraine in Patients With Unsuccessful Prior Preventive Treatments graded on: randomised and placebo-controlled — “Randomized, Double-blind, Parallel-group, Placebo-controlled”
animal in vivo
Differential signal transduction by five splice variants of the PACAP receptor (Nature 1993, cited 996x) graded on: an animal model — read from the indexed abstract — “rats”
animal in vivo
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor (Nature 2011, cited 727x) graded on: an animal model — read from the indexed abstract — “rats”

Not graded

1 citation whose study design could not be read from the title. Left ungraded rather than guessed at.

not graded
NCT07342296: Induction of Migraine Attacks With Aura Using Pituitary Adenylate Cyclase Activating Polypeptide-38: A Randomized Clinical Trial graded on: NCT07342296 is not yet recruiting and has posted no results - a registration, not a reported outcome — “NCT07342296”

Identity

Space-filling 3D model of PACAP (Pituitary Adenylate Cyclase-Activating Peptide), carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of PACAP (Pituitary Adenylate Cyclase-Activating Peptide) — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 4435
Molecular formula: C199H322N60O53S
CAS number: 137061-48-4
PubChem CID: 133082079
UniProt: P18509 (precursor)
InChI key: SIOKKMOWMDCVKB-RGBLINGASA-N
SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC5=CC=C(C=C5)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)N)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CN=CN6)N
InChI: InChI=1S/C199H322N60O53S/c1-18-107(12)160(255-154(273)97-224-169(285)144(92-155(274)275)248-190(306)146(98-260)252-166(282)122(207)90-117-94-218-101-225-117)195(311)250-142(85-112-39-20-19-21-40-112)188(304)259-161(111(16)263)196(312)251-145(93-156(276)277)187(303)254-148(100-262)191(307)246-141(89-116-57-65-121(267)66-58-116)185(301)253-147(99-261)189(305)237-131(49-37-80-220-198(214)215)177(293)244-139(87-114-53-61-119(265)62-54-114)183(299)236-130(48-36-79-219-197(212)213)174(290)232-125(43-24-31-74-202)171(287)239-134(68-70-150(209)269)179(295)240-135(71-82-313-17)170(286)227-110(15)165(281)256-157(104(6)7)192(308)241-128(46-27-34-77-205)173(289)233-127(45-26-33-76-204)175(291)245-140(88-115-55-63-120(266)64-56-115)184(300)243-137(84-103(4)5)181(297)228-108(13)163(279)226-109(14)164(280)257-158(105(8)9)194(310)249-136(83-102(2)3)168(284)223-95-152(271)229-124(42-23-30-73-201)167(283)222-96-153(272)230-138(86-113-51-59-118(264)60-52-113)182(298)235-126(44-25-32-75-203)172(288)238-133(67-69-149(208)268)178(294)234-132(50-38-81-221-199(216)217)180(296)258-159(106(10)11)193(309)242-129(47-28-35-78-206)176(292)247-143(91-151(210)270)186(302)231-123(162(211)278)41-22-29-72-200/h19-21,39-40,51-66,94,101-111,122-148,157-161,260-267H,18,22-38,41-50,67-93,95-100,200-207H2,1-17H3,(H2,208,268)(H2,209,269)(H2,210,270)(H2,211,278)(H,218,225)(H,222,283)(H,223,284)(H,224,285)(H,226,279)(H,227,286)(H,228,297)(H,229,271)(H,230,272)(H,231,302)(H,232,290)(H,233,289)(H,234,294)(H,235,298)(H,236,299)(H,237,305)(H,238,288)(H,239,287)(H,240,295)(H,241,308)(H,242,309)(H,243,300)(H,244,293)(H,245,291)(H,246,307)(H,247,292)(H,248,306)(H,249,310)(H,250,311)(H,251,312)(H,252,282)(H,253,301)(H,254,303)(H,255,273)(H,256,281)(H,257,280)(H,258,296)(H,259,304)(H,274,275)(H,276,277)(H4,212,213,219)(H4,214,215,220)(H4,216,217,221)/t107-,108-,109-,110-,111+,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-,157-,158-,159-,160-,161-/m0/s1

Also called

PACAP
PACAP (Research)

Caveat on these identifiers

NCT05133323 tests an ANTI-PACAP antibody (Lu AG09222), not PACAP administration. Source files disagreed on evidence tier for this peptide.

Notes unverified prose

NCT07342296; Phase 2 HOPE trial (NCT05133323); NCT07342296 (PACAP-38 migraine induction); LY3451838 1,500 mg IV for migraine; Phase 2 HOPE trial (Lu AG09222); LY3451838 Phase 1/2

Not on file 2

1 of the 8 fields we track hold nothing on this record, and each says why. 1 further absence is named below. A blank field is a bug; a named absence is a finding.

amino-acid sequencenothing we hold supplies it
half-lifenothing we hold supplies it

Each field links to every other record missing the same thing. The full ledger holds 765 gaps across 163 records.