CALCB

Summary

CALCB (calcitonin related polypeptide beta, HGNC:1438) is a protein-coding gene on chromosome 11p15.2, encoding Calcitonin gene-related peptide 2 (P10092). CALCB/CGRP2 is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex.

Enables hormone activity. Involved in calcitonin gene-related peptide receptor signaling pathway. Is active in extracellular space.

Source: NCBI Gene 797 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_000728

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1438
Approved symbol	CALCB
Name	calcitonin related polypeptide beta
Location	11p15.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30166, CGRP-II
Ensembl gene	ENSG00000175868
Ensembl biotype	protein_coding
OMIM	114160
Entrez	797

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000324229, ENST00000523376, ENST00000533448, ENST00000887807, ENST00000887808, ENST00000918239, ENST00000918240, ENST00000918241, ENST00000918242

RefSeq mRNA: 1 — MANE Select: NM_000728 NM_000728

CCDS: CCDS7820

Canonical transcript exons

ENST00000324229 — 5 exons

Exon	Start	End
ENSE00001004431	15075061	15075198
ENSE00001300426	15077286	15077470
ENSE00001426742	15078083	15078637
ENSE00003509258	15074710	15074804
ENSE00003846628	15073593	15073663

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 97.24.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2917 / max 444.7326, expressed in 198 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113230	1.2030	152
113229	0.0888	43

Top tissues by expression

259 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	97.24	gold quality
trigeminal ganglion	UBERON:0001675	89.15	gold quality
islet of Langerhans	UBERON:0000006	77.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.34	gold quality
hypothalamus	UBERON:0001898	68.34	gold quality
pancreas	UBERON:0001264	65.91	gold quality
adenohypophysis	UBERON:0002196	64.42	gold quality
body of pancreas	UBERON:0001150	61.89	gold quality
periodontal ligament	UBERON:0008266	61.24	gold quality
pituitary gland	UBERON:0000007	60.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.68	gold quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	56.43	silver quality
hair follicle	UBERON:0002073	56.10	gold quality
sigmoid colon	UBERON:0001159	55.30	gold quality
pigmented layer of retina	UBERON:0001782	55.11	gold quality
spinal cord	UBERON:0002240	54.76	gold quality
prefrontal cortex	UBERON:0000451	54.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	54.62	gold quality
endometrium epithelium	UBERON:0004811	54.47	gold quality
cerebellar cortex	UBERON:0002129	53.56	gold quality
cerebellar hemisphere	UBERON:0002245	53.53	gold quality
cerebellum	UBERON:0002037	52.70	gold quality
vena cava	UBERON:0004087	52.29	gold quality
cortex of kidney	UBERON:0001225	51.89	gold quality
choroid plexus epithelium	UBERON:0003911	51.79	silver quality
right hemisphere of cerebellum	UBERON:0014890	51.66	gold quality
metanephros	UBERON:0000081	51.43	gold quality
metanephros cortex	UBERON:0010533	51.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	7.41
E-ANND-3	no	4.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN, NFKB

miRNA regulators (miRDB)

60 targeting CALCB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4719	99.73	72.10	3329

Literature-anchored findings (GeneRIF, showing 5)

• CGRP and ADM are two differentially regulated novel adipose tissue secretion factors exerting autocrine/paracrine roles. (PMID:15761041)
• Calcitonin gene-related peptide stimulates proliferation of alveolar epithelial cells. (PMID:19192276)
• Keratinocyte-derived CGRPbeta may modulate epidermal homeostasis through autocrine/paracrine signaling and may contribute to chronic pain under pathological conditions. (PMID:21641113)
• The results suggest that C12orf39, CSTA, and CALCB are novel ATF4 target genes, and that C12orf39 promoter activity is activated by ATF4 through amino acid response element. (PMID:26967115)
• CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland. (PMID:34234876)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	calca	ENSDARG00000056590
mus_musculus	Calcb	ENSMUSG00000030666
rattus_norvegicus	Calcb	ENSRNOG00000011074

Paralogs (2): CALCA (ENSG00000110680), IAPP (ENSG00000121351)

Protein

Protein identifiers

Calcitonin gene-related peptide 2 — P10092 (reviewed: P10092)

Alternative names: Beta-type CGRP, Calcitonin gene-related peptide II

All UniProt accessions (2): E7ESF5, P10092

UniProt curated annotations — full annotation on UniProt →

Function. CALCB/CGRP2 is a peptide hormone that induces vasodilation mediated by the CALCRL-RAMP1 receptor complex. Dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Subcellular location. Secreted.

Tissue specificity. Expressed in spinal cord, pituitary and thalamus.

Similarity. Belongs to the calcitonin family.

RefSeq proteins (1): NP_000719* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001693	Calcitonin_peptide-like	Domain
IPR015476	Calcitonin_gene-rel_peptide	Family
IPR018360	Calcitonin_CS	Conserved_site
IPR021116	Calcitonin/adrenomedullin	Family
IPR021117	Calcitonin-like	Family

Pfam: PF00214

UniProt features (7 total): propeptide 2, signal peptide 1, peptide 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10092-F1	71.15	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 118

Disulfide bonds (1): 83–88

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-419812	Calcitonin-like ligand receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 96 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, TGACCTY_ERR1_Q2, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, JEON_SMAD6_TARGETS_DN, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_BINDING, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOBP_ADENYLATE_CYCLASE_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (6): intracellular calcium ion homeostasis (GO:0006874), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), regulation of cytosolic calcium ion concentration (GO:0051480), calcitonin gene-related peptide receptor signaling pathway (GO:1990408), calcitonin family receptor signaling pathway (GO:0097646)

GO Molecular Function (5): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), calcitonin receptor binding (GO:0031716), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
intracellular calcium ion homeostasis	1
calcitonin family receptor signaling pathway	1
G protein-coupled receptor signaling pathway	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
G protein-coupled receptor binding	1
binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALCB	RAMP1	O60894	965
CALCB	CALCRL	Q16602	957
CALCB	IAPP	P10997	949
CALCB	RAMP3	O60896	933
CALCB	ADM	P35318	918
CALCB	RAMP2	O60895	907
CALCB	CALCR	P30988	879
CALCB	MICU1	Q9BPX6	711
CALCB	ADM2	Q7Z4H4	667
CALCB	TAC1	P20366	614
CALCB	TRPV1	Q8NER1	525
CALCB	GAL	P22466	454
CALCB	TACR1	P25103	447
CALCB	CRCP	O75575	445
CALCB	VIP	P01282	439

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CALCB	CIB1	psi-mi:“MI:0915”(physical association)	0.560
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
ZNF212	CALCB	psi-mi:“MI:0915”(physical association)	0.400
GINM1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
GINM1	FAM234B	psi-mi:“MI:0914”(association)	0.350
GIP	GNPAT	psi-mi:“MI:0914”(association)	0.350
ACTA2	GSN	psi-mi:“MI:0914”(association)	0.350
ANKEF1	CALCB	psi-mi:“MI:0914”(association)	0.350
ATG14	CALCB	psi-mi:“MI:0914”(association)	0.350
CALCB	CIB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-RNA), CIB1 (Two-hybrid), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-MS), CALCB (Affinity Capture-RNA)

ESM2 similar proteins: A0A1L2F565, B3IWF8, O09163, O57312, O73812, O93464, P01189, P01193, P01194, P01256, P01355, P01356, P04089, P06307, P06881, P07660, P09240, P10092, P10093, P10286, P12760, P23362, P37042, P41520, P45656, P48645, P55247, P81564, P81872, P87352, Q28588, Q75V93, Q75V94, Q766Y6, Q766Y7, Q805D3, Q862B1, Q90Y63, Q91082, Q99JA0

Diamond homologs: B3IWF7, B3IWF8, B3IWF9, P01256, P01257, P01258, P01261, P06881, P07660, P10092, P10093, P10286, P12966, P12967, P12969, P17716, P22889, P30880, P30881, P31888, P41547, P70160, Q28207, Q75V93, Q75V94, Q75V95, Q766Y6, Q766Y7, Q862B1, Q99JA0, Q99MP3, Q9MYV1, Q9N0T2, Q9N0T3, Q9N0V5, P01263, P81564, P10997, P12968, P19890

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1107 predictions. Top by Δscore:

Variant	Effect	Δscore
11:14967863:CAGGA:C	acceptor_gain	1.0000
11:14967864:A:T	acceptor_gain	1.0000
11:14967867:A:AC	acceptor_gain	1.0000
11:14967867:A:C	acceptor_gain	1.0000
11:14970071:CAGAC:C	acceptor_gain	1.0000
11:14970072:AGAC:A	acceptor_gain	1.0000
11:14970073:GAC:G	acceptor_gain	1.0000
11:14970073:GACC:G	acceptor_loss	1.0000
11:14970074:AC:A	acceptor_gain	1.0000
11:14970074:ACCT:A	acceptor_loss	1.0000
11:14970075:CC:C	acceptor_gain	1.0000
11:14970075:CCTG:C	acceptor_loss	1.0000
11:14970076:C:CC	acceptor_gain	1.0000
11:15074709:GA:G	acceptor_gain	1.0000
11:15075194:TCCAG:T	donor_loss	1.0000
11:15075195:CCAG:C	donor_loss	1.0000
11:15075197:AGG:A	donor_loss	1.0000
11:15075198:GGTGA:G	donor_loss	1.0000
11:15075199:G:GC	donor_loss	1.0000
11:15075200:T:G	donor_loss	1.0000
11:15077272:A:AG	acceptor_gain	1.0000
11:15077272:ATCTT:A	acceptor_gain	1.0000
11:15077273:T:G	acceptor_gain	1.0000
11:15077276:T:A	acceptor_gain	1.0000
11:15077279:A:AG	acceptor_gain	1.0000
11:15077280:A:G	acceptor_gain	1.0000
11:15077282:TCA:T	acceptor_loss	1.0000
11:15077284:A:AG	acceptor_gain	1.0000
11:15077285:G:GA	acceptor_gain	1.0000
11:15077285:GC:G	acceptor_gain	1.0000

AlphaMissense

822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:15077413:T:C	F118L	0.979
11:15077415:T:A	F118L	0.979
11:15077415:T:G	F118L	0.979
11:15077309:G:A	C83Y	0.935
11:15077323:T:C	C88R	0.934
11:15077310:C:G	C83W	0.932
11:15077325:T:G	C88W	0.929
11:15074755:A:C	S13R	0.925
11:15074757:T:A	S13R	0.925
11:15074757:T:G	S13R	0.925
11:15077308:T:C	C83R	0.925
11:15077339:T:C	L93P	0.924
11:15077336:G:C	R92P	0.923
11:15077323:T:A	C88S	0.920
11:15077324:G:C	C88S	0.920
11:15077383:T:C	F108L	0.915
11:15077385:C:A	F108L	0.915
11:15077385:C:G	F108L	0.915
11:15077417:G:A	G119D	0.915
11:15077324:G:A	C88Y	0.911
11:15077309:G:T	C83F	0.905
11:15077393:C:T	T111I	0.902
11:15077341:G:C	A94P	0.901
11:15077339:T:A	L93Q	0.900
11:15077351:T:A	L97Q	0.900
11:15077308:T:A	C83S	0.897
11:15077309:G:C	C83S	0.897
11:15077324:G:T	C88F	0.896
11:15077351:T:C	L97P	0.892
11:15077414:T:G	F118C	0.887

dbSNP variants (sampled 300 via entrez): RS1000390208 (11:15071645 C>A,T), RS1000828768 (11:15075828 G>T), RS1000932244 (11:15076110 G>C), RS1001162151 (11:15074384 A>C,G), RS1001276587 (11:15074692 G>A,C), RS1001363140 (11:15075801 G>A), RS1002148091 (11:15076894 CTTCT>C), RS1002832346 (11:15073079 A>G), RS1002948744 (11:15073225 C>A), RS1003030638 (11:15078685 T>A), RS1003164272 (11:15071981 C>G), RS1003280599 (11:15072210 G>A,C), RS1003729420 (11:15078119 T>A), RS1005046817 (11:15079117 C>T), RS1005401459 (11:15078014 C>T)

Disease associations

OMIM: gene MIM:114160 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008256_1	Diverticulitis	4.000000e-07
GCST90020028_1979	Hip circumference adjusted for BMI	2.000000e-12
GCST90020028_1980	Hip circumference adjusted for BMI	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3713541 (SINGLE PROTEIN), CHEMBL3832947 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.20	IC50	0.631	nM	CHEMBL4873687
9.00	IC50	1	nM	CHEMBL4851152
8.90	IC50	1.259	nM	CHEMBL4850259
8.70	IC50	1.995	nM	CHEMBL4877585
8.60	IC50	2.512	nM	CHEMBL4879142
8.50	IC50	3.162	nM	CHEMBL4850583
8.40	IC50	3.981	nM	CHEMBL4871934
8.40	IC50	3.981	nM	CHEMBL4857810
8.30	IC50	5.012	nM	CHEMBL4866915
8.30	IC50	5.012	nM	CHEMBL4852669
8.30	IC50	5.012	nM	CHEMBL4861626
8.10	IC50	7.943	nM	CHEMBL4866548
8.10	IC50	7.943	nM	CHEMBL4874651
7.60	IC50	25.12	nM	CHEMBL4862324
7.30	IC50	50.12	nM	CHEMBL4876643
7.00	IC50	100	nM	CHEMBL4851106
7.00	IC50	100	nM	CHEMBL4870543
7.00	IC50	100	nM	CHEMBL4878394
6.90	IC50	125.9	nM	CHEMBL4856402
6.70	IC50	199.5	nM	CHEMBL4853766
6.40	IC50	398.1	nM	CHEMBL4874859
6.30	IC50	501.2	nM	CHEMBL4865654
6.10	IC50	794.3	nM	CHEMBL4846989
5.50	IC50	3162	nM	CHEMBL4876213

PubChem BioAssay actives

24 with measured affinity, of 24 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[[2-[(diaminomethylideneamino)methyl]phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0006	uM
N-[[2-[(cyclopropylamino)methyl]phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0010	uM
N-[[2-(1-aminoethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0013	uM
N-[[2-(azetidin-1-ylmethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0020	uM
N-[[2-(2-aminoethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0025	uM
N-[[2-(imidazol-1-ylmethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0032	uM
N-[(2-aminophenyl)methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0040	uM
2,2-dimethyl-N-[[2-(methylaminomethyl)phenyl]methyl]-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0040	uM
N-[[2-(aminomethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0050	uM
N-[[2-(hydroxymethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0050	uM
N-(1H-indazol-4-ylmethyl)-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0050	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-[(2-pyrrolidin-3-ylphenyl)methyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0079	uM
2,2-dimethyl-N-[[2-(morpholin-4-ylmethyl)phenyl]methyl]-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0079	uM
N-[(2-cyanophenyl)methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0251	uM
2-[[2,2-dimethylpropanoyl-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]amino]methyl]benzamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.0501	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-(pyridin-2-ylmethyl)propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.1000	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-[(2-phenylpyrazol-3-yl)methyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.1000	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-(1,3-thiazol-2-ylmethyl)propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.1000	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-(1,2,3,4-tetrahydroisoquinolin-8-ylmethyl)propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.1259	uM
N-[1-[2-(aminomethyl)phenyl]ethyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.1995	uM
2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]-N-[(2-pyridin-3-ylphenyl)methyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.3981	uM
N-[[3-(aminomethyl)-2-pyridinyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.5012	uM
N-[[3-(aminomethyl)phenyl]methyl]-2,2-dimethyl-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	0.7943	uM
2,2-dimethyl-N-[(1-methylpiperidin-3-yl)methyl]-N-[2-oxo-2-[(2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl)amino]ethyl]propanamide	1761961: Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay	ic50	3.1623	uM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	8
Capsaicin	increases secretion, decreases reaction, decreases activity, increases expression	3
Cisplatin	affects response to substance, affects cotreatment, decreases expression	2
Tunicamycin	increases expression	2
tungsten carbide	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
hydroquinone	increases expression	1
capsazepine	decreases reaction, increases expression	1
fipronil	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cobalt	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Dactinomycin	affects cotreatment, increases expression	1
DEET	affects cotreatment, increases expression	1
Diethylnitrosamine	increases expression	1
Disulfiram	affects binding, decreases expression	1
Tretinoin	affects expression	1
Thapsigargin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4820959	Binding	Antagonist activity at human CGRP-2 (8 to 37 residues) expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15	Discovery of a First-In-Class Small Molecule Antagonist against the Adrenomedullin-2 Receptor: Structure-Activity Relationships and Optimization. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.