NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	386.93
Volume:	262.302
LogP:	1.786
LogD:	1.381
LogS:	-2.889
# Rotatable Bonds:	1
TPSA:	100.32
# H-Bond Aceptor:	6
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.506
Synthetic Accessibility Score:	4.527
Fsp3:	0.273
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.375
MDCK Permeability:	8.260539289040025e-06
Pgp-inhibitor:	0.001
Pgp-substrate:	0.051
Human Intestinal Absorption (HIA):	0.916
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.196
Plasma Protein Binding (PPB):	91.42150115966797%
Volume Distribution (VD):	0.78
Pgp-substrate:	11.132617950439453%

ADMET: Metabolism

CYP1A2-inhibitor:	0.053
CYP1A2-substrate:	0.942
CYP2C19-inhibitor:	0.468
CYP2C19-substrate:	0.042
CYP2C9-inhibitor:	0.236
CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	0.011
CYP2D6-substrate:	0.059
CYP3A4-inhibitor:	0.708
CYP3A4-substrate:	0.589

ADMET: Excretion

Clearance (CL):	4.083
Half-life (T1/2):	0.851

ADMET: Toxicity

hERG Blockers:	0.751
Human Hepatotoxicity (H-HT):	0.982
Drug-inuced Liver Injury (DILI):	0.916
AMES Toxicity:	0.181
Rat Oral Acute Toxicity:	0.989
Maximum Recommended Daily Dose:	0.967
Skin Sensitization:	0.471
Carcinogencity:	0.692
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.974

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC469976

Natural Product ID:	NPC469976
*Common Name:**	4-(2-Amino-1H-Imidazol-5-Yl)-2,3-Dibromo-4,5,6,7-Tetrahydro-1H-Pyrrolo[2,3-C]Azepin-8-One
IUPAC Name:	4-(2-amino-1H-imidazol-5-yl)-2,3-dibromo-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]azepin-8-one
Synonyms:
Standard InCHIKey:	MRMGABUTBNWSLA-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C11H11Br2N5O/c12-7-6-4(5-3-16-11(14)17-5)1-2-15-10(19)8(6)18-9(7)13/h3-4,18H,1-2H2,(H,15,19)(H3,14,16,17)
SMILES:	O=C1NCCC(c2c1[nH]c(c2Br)Br)c1c[nH]c(=N)[nH]1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL151430
PubChem CID:	9930243
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001990] Pyrroloazepines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO7079	Stylissa massa	Species	Axinellidae	Eukaryota	n.a.	Philippine	n.a.	PMID[11784156]
NPO7079	Stylissa massa	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12816422]
NPO7079	Stylissa massa	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[23684893]
NPO7079	Stylissa massa	Species	Axinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	6

Activity Type	# Activity
Cell Line	2
Individual Protein	3
Protein Family	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT491	Individual Protein	Dual specificity mitogen-activated protein kinase kinase 1	Homo sapiens	IC50	=	2500.0	nM	PMID[484692]
NPT282	Individual Protein	MAP kinase ERK2	Homo sapiens	IC50	=	1288.0	nM	PMID[484692]
NPT492	Cell Line	Caco-2	Homo sapiens	IC50	>	10000.0	nM	PMID[484692]
NPT114	Cell Line	LoVo	Homo sapiens	IC50	>	10000.0	nM	PMID[484692]
NPT491	Individual Protein	Dual specificity mitogen-activated protein kinase kinase 1	Homo sapiens	IC50	=	6.0	nM	PMID[484693]
NPT490	Protein Family	Serine/threonine-protein kinase RAF and Dual specificity mitogen-activated protein kinase kinase 1 (Raf/MEK)	Homo sapiens	IC50	=	1288.0	nM	PMID[484692]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC469976 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	1584
0.1-0.2	16159
0.2-0.3	17725
0.3-0.4	2903
0.4-0.5	2451
0.5-0.6	1438
0.6-0.7	347
0.7-0.8	71
0.8-0.85	11
0.85-0.9	6
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9299	High Similarity	NPC73687
0.9074	High Similarity	NPC271927
0.8827	High Similarity	NPC474696
0.875	High Similarity	NPC472861
0.875	High Similarity	NPC184932
0.8704	High Similarity	NPC206148
0.8452	Intermediate Similarity	NPC37268
0.8362	Intermediate Similarity	NPC19342
0.8229	Intermediate Similarity	NPC111566
0.8182	Intermediate Similarity	NPC310633
0.8132	Intermediate Similarity	NPC136957
0.8132	Intermediate Similarity	NPC19696
0.8125	Intermediate Similarity	NPC63571
0.8118	Intermediate Similarity	NPC54214
0.8066	Intermediate Similarity	NPC476526
0.8066	Intermediate Similarity	NPC48117
0.8066	Intermediate Similarity	NPC329765
0.8022	Intermediate Similarity	NPC174281
0.8022	Intermediate Similarity	NPC475286
0.7988	Intermediate Similarity	NPC2414
0.7719	Intermediate Similarity	NPC476418
0.7701	Intermediate Similarity	NPC227489
0.7701	Intermediate Similarity	NPC28096
0.7701	Intermediate Similarity	NPC476421
0.7696	Intermediate Similarity	NPC476525
0.7696	Intermediate Similarity	NPC476524
0.766	Intermediate Similarity	NPC9635
0.76	Intermediate Similarity	NPC226835
0.7571	Intermediate Similarity	NPC136441
0.7557	Intermediate Similarity	NPC80528
0.7527	Intermediate Similarity	NPC476527
0.7514	Intermediate Similarity	NPC97106
0.747	Intermediate Similarity	NPC260041
0.7437	Intermediate Similarity	NPC469717
0.7391	Intermediate Similarity	NPC150592
0.7344	Intermediate Similarity	NPC469716
0.7316	Intermediate Similarity	NPC474389
0.7273	Intermediate Similarity	NPC233380
0.7234	Intermediate Similarity	NPC476413
0.7228	Intermediate Similarity	NPC469814
0.7222	Intermediate Similarity	NPC20021
0.7196	Intermediate Similarity	NPC188821
0.7196	Intermediate Similarity	NPC474180
0.7196	Intermediate Similarity	NPC476414
0.7186	Intermediate Similarity	NPC469715
0.7127	Intermediate Similarity	NPC186068
0.7086	Intermediate Similarity	NPC27296
0.6971	Remote Similarity	NPC474236
0.6931	Remote Similarity	NPC473946
0.6927	Remote Similarity	NPC306160
0.6927	Remote Similarity	NPC274981
0.6915	Remote Similarity	NPC476423
0.6915	Remote Similarity	NPC474258
0.6897	Remote Similarity	NPC471655
0.6889	Remote Similarity	NPC474383
0.6878	Remote Similarity	NPC46022
0.6878	Remote Similarity	NPC112489
0.6865	Remote Similarity	NPC240088
0.6865	Remote Similarity	NPC473380
0.6837	Remote Similarity	NPC477004
0.6814	Remote Similarity	NPC470703
0.6765	Remote Similarity	NPC470702
0.6765	Remote Similarity	NPC473218
0.676	Remote Similarity	NPC474492
0.6738	Remote Similarity	NPC265710
0.6722	Remote Similarity	NPC473706
0.6702	Remote Similarity	NPC234403
0.6702	Remote Similarity	NPC16659
0.6683	Remote Similarity	NPC475736
0.6648	Remote Similarity	NPC247987
0.6633	Remote Similarity	NPC13456
0.6633	Remote Similarity	NPC166209
0.6633	Remote Similarity	NPC77241
0.6633	Remote Similarity	NPC46811
0.6633	Remote Similarity	NPC269203
0.663	Remote Similarity	NPC100104
0.663	Remote Similarity	NPC470680
0.6619	Remote Similarity	NPC474195
0.6614	Remote Similarity	NPC79777
0.6583	Remote Similarity	NPC268744
0.6583	Remote Similarity	NPC474318
0.6583	Remote Similarity	NPC475914
0.6583	Remote Similarity	NPC237414
0.6583	Remote Similarity	NPC153123
0.6583	Remote Similarity	NPC201266
0.6583	Remote Similarity	NPC220797
0.6562	Remote Similarity	NPC133003
0.6536	Remote Similarity	NPC232798
0.6526	Remote Similarity	NPC314281
0.6526	Remote Similarity	NPC40530
0.6519	Remote Similarity	NPC475870
0.6514	Remote Similarity	NPC474357
0.651	Remote Similarity	NPC21429
0.651	Remote Similarity	NPC477003
0.6498	Remote Similarity	NPC470323
0.6497	Remote Similarity	NPC100726
0.6495	Remote Similarity	NPC474196
0.648	Remote Similarity	NPC472260
0.6468	Remote Similarity	NPC935
0.6468	Remote Similarity	NPC267078
0.6462	Remote Similarity	NPC473628
0.646	Remote Similarity	NPC66642
0.6459	Remote Similarity	NPC50562
0.6443	Remote Similarity	NPC141612
0.6443	Remote Similarity	NPC135601
0.6443	Remote Similarity	NPC17273
0.644	Remote Similarity	NPC182940
0.6433	Remote Similarity	NPC291517
0.6429	Remote Similarity	NPC324091
0.6429	Remote Similarity	NPC475874
0.6429	Remote Similarity	NPC67658
0.6425	Remote Similarity	NPC110158
0.6425	Remote Similarity	NPC473878
0.6408	Remote Similarity	NPC116555
0.64	Remote Similarity	NPC129412
0.64	Remote Similarity	NPC101130
0.64	Remote Similarity	NPC58268
0.64	Remote Similarity	NPC114033
0.6383	Remote Similarity	NPC262338
0.6373	Remote Similarity	NPC470205
0.6369	Remote Similarity	NPC102664
0.6354	Remote Similarity	NPC477042
0.6349	Remote Similarity	NPC161861
0.6344	Remote Similarity	NPC280864
0.6344	Remote Similarity	NPC17751
0.6341	Remote Similarity	NPC473376
0.6337	Remote Similarity	NPC23215
0.6332	Remote Similarity	NPC221726
0.6332	Remote Similarity	NPC225622
0.6332	Remote Similarity	NPC477414
0.633	Remote Similarity	NPC156003
0.6321	Remote Similarity	NPC307191
0.6313	Remote Similarity	NPC476460
0.6313	Remote Similarity	NPC210123
0.6313	Remote Similarity	NPC243716
0.6308	Remote Similarity	NPC311282
0.6296	Remote Similarity	NPC302647
0.6293	Remote Similarity	NPC317701
0.6292	Remote Similarity	NPC204141
0.6292	Remote Similarity	NPC470440
0.6283	Remote Similarity	NPC151635
0.6269	Remote Similarity	NPC102592
0.6269	Remote Similarity	NPC79356
0.625	Remote Similarity	NPC175150
0.625	Remote Similarity	NPC243633
0.625	Remote Similarity	NPC284775
0.6243	Remote Similarity	NPC52110
0.6237	Remote Similarity	NPC191415
0.6237	Remote Similarity	NPC253687
0.6232	Remote Similarity	NPC471191
0.6224	Remote Similarity	NPC99939
0.6224	Remote Similarity	NPC308931
0.6223	Remote Similarity	NPC109447
0.6218	Remote Similarity	NPC11126
0.6209	Remote Similarity	NPC217021
0.6209	Remote Similarity	NPC470679
0.6207	Remote Similarity	NPC98156
0.6207	Remote Similarity	NPC138596
0.6207	Remote Similarity	NPC200397
0.6207	Remote Similarity	NPC195704
0.6207	Remote Similarity	NPC64661
0.6207	Remote Similarity	NPC14448
0.6207	Remote Similarity	NPC167200
0.6207	Remote Similarity	NPC292434
0.6205	Remote Similarity	NPC102755
0.6203	Remote Similarity	NPC162268
0.6196	Remote Similarity	NPC142688
0.6196	Remote Similarity	NPC74357
0.6188	Remote Similarity	NPC123906
0.6186	Remote Similarity	NPC168209
0.6186	Remote Similarity	NPC88110
0.6175	Remote Similarity	NPC251391
0.6173	Remote Similarity	NPC228835
0.6171	Remote Similarity	NPC125746
0.6168	Remote Similarity	NPC267811
0.6158	Remote Similarity	NPC169308
0.6158	Remote Similarity	NPC209281
0.6158	Remote Similarity	NPC77582
0.6158	Remote Similarity	NPC302717
0.6158	Remote Similarity	NPC129753
0.6158	Remote Similarity	NPC97230
0.6158	Remote Similarity	NPC244087
0.6158	Remote Similarity	NPC205604
0.6158	Remote Similarity	NPC3698
0.6158	Remote Similarity	NPC74928
0.6158	Remote Similarity	NPC471943
0.6158	Remote Similarity	NPC59839
0.6158	Remote Similarity	NPC286529
0.6158	Remote Similarity	NPC48171
0.6158	Remote Similarity	NPC12831
0.6146	Remote Similarity	NPC469529
0.6146	Remote Similarity	NPC280297
0.6138	Remote Similarity	NPC49217
0.6132	Remote Similarity	NPC471194
0.6132	Remote Similarity	NPC471193
0.6122	Remote Similarity	NPC270834
0.6119	Remote Similarity	NPC477166
0.6119	Remote Similarity	NPC477167
0.6119	Remote Similarity	NPC473342
0.6119	Remote Similarity	NPC304187

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC469976 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	376
0.1-0.2	1121
0.2-0.3	1731
0.3-0.4	2235
0.4-0.5	2045
0.5-0.6	1332
0.6-0.7	293
0.7-0.8	17
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.652	Remote Similarity	NPD1506	Discontinued
0.6515	Remote Similarity	NPD2289	Phase 3
0.6515	Remote Similarity	NPD2290	Phase 3
0.6488	Remote Similarity	NPD2442	Approved
0.6488	Remote Similarity	NPD2443	Approved
0.6458	Remote Similarity	NPD3318	Approved
0.6458	Remote Similarity	NPD3319	Phase 1
0.6458	Remote Similarity	NPD3320	Approved
0.6377	Remote Similarity	NPD2408	Discontinued
0.6368	Remote Similarity	NPD7459	Phase 2
0.6364	Remote Similarity	NPD7656	Approved
0.6364	Remote Similarity	NPD7657	Approved
0.6345	Remote Similarity	NPD5685	Approved
0.6345	Remote Similarity	NPD5686	Approved
0.6332	Remote Similarity	NPD460	Discontinued
0.6327	Remote Similarity	NPD2009	Clinical (unspecified phase)
0.6318	Remote Similarity	NPD1952	Discontinued
0.6313	Remote Similarity	NPD5592	Clinical (unspecified phase)
0.6287	Remote Similarity	NPD465	Clinical (unspecified phase)
0.6284	Remote Similarity	NPD276	Clinical (unspecified phase)
0.6262	Remote Similarity	NPD5199	Approved
0.6262	Remote Similarity	NPD5198	Approved
0.6256	Remote Similarity	NPD2405	Phase 3
0.625	Remote Similarity	NPD5001	Clinical (unspecified phase)
0.6238	Remote Similarity	NPD2880	Discontinued
0.6232	Remote Similarity	NPD2008	Discontinued
0.622	Remote Similarity	NPD1600	Suspended
0.6209	Remote Similarity	NPD9343	Clinical (unspecified phase)
0.6207	Remote Similarity	NPD1982	Phase 1
0.6202	Remote Similarity	NPD8493	Clinical (unspecified phase)
0.6193	Remote Similarity	NPD5820	Clinical (unspecified phase)
0.615	Remote Similarity	NPD1658	Discontinued
0.6132	Remote Similarity	NPD2411	Approved
0.6129	Remote Similarity	NPD2214	Approved
0.6129	Remote Similarity	NPD2213	Approved
0.6117	Remote Similarity	NPD6837	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD4426	Clinical (unspecified phase)
0.6106	Remote Similarity	NPD6288	Clinical (unspecified phase)
0.6102	Remote Similarity	NPD569	Clinical (unspecified phase)
0.6093	Remote Similarity	NPD5643	Phase 2
0.608	Remote Similarity	NPD3246	Discontinued
0.6071	Remote Similarity	NPD3178	Discontinued
0.6071	Remote Similarity	NPD1783	Clinical (unspecified phase)
0.607	Remote Similarity	NPD6180	Clinical (unspecified phase)
0.6066	Remote Similarity	NPD7704	Clinical (unspecified phase)
0.605	Remote Similarity	NPD1284	Clinical (unspecified phase)
0.6048	Remote Similarity	NPD6328	Clinical (unspecified phase)
0.6042	Remote Similarity	NPD3347	Clinical (unspecified phase)
0.604	Remote Similarity	NPD4922	Phase 2
0.601	Remote Similarity	NPD1096	Discontinued
0.6009	Remote Similarity	NPD4863	Approved
0.6009	Remote Similarity	NPD3915	Approved
0.6	Remote Similarity	NPD5446	Phase 2
0.6	Remote Similarity	NPD7971	Clinical (unspecified phase)
0.6	Remote Similarity	NPD6664	Approved
0.6	Remote Similarity	NPD7970	Approved
0.5981	Remote Similarity	NPD3918	Approved
0.5981	Remote Similarity	NPD3916	Clinical (unspecified phase)
0.5981	Remote Similarity	NPD3917	Approved
0.5969	Remote Similarity	NPD2590	Clinical (unspecified phase)
0.5965	Remote Similarity	NPD3360	Clinical (unspecified phase)
0.5962	Remote Similarity	NPD7817	Phase 1
0.5961	Remote Similarity	NPD7098	Clinical (unspecified phase)
0.5949	Remote Similarity	NPD2367	Phase 2
0.5936	Remote Similarity	NPD1996	Discontinued
0.5935	Remote Similarity	NPD8013	Clinical (unspecified phase)
0.5933	Remote Similarity	NPD6802	Phase 3
0.593	Remote Similarity	NPD3607	Clinical (unspecified phase)
0.5924	Remote Similarity	NPD3967	Approved
0.5918	Remote Similarity	NPD3041	Approved
0.5912	Remote Similarity	NPD2007	Clinical (unspecified phase)
0.5902	Remote Similarity	NPD5855	Phase 3
0.5902	Remote Similarity	NPD7618	Phase 3
0.5902	Remote Similarity	NPD5853	Phase 3
0.5902	Remote Similarity	NPD7619	Phase 3
0.5896	Remote Similarity	NPD3410	Approved
0.5896	Remote Similarity	NPD3411	Phase 2
0.5891	Remote Similarity	NPD7175	Phase 1
0.5888	Remote Similarity	NPD3079	Approved
0.5888	Remote Similarity	NPD3077	Approved
0.5888	Remote Similarity	NPD7809	Clinical (unspecified phase)
0.5888	Remote Similarity	NPD3078	Approved
0.5888	Remote Similarity	NPD3076	Approved
0.5885	Remote Similarity	NPD3891	Phase 2
0.5885	Remote Similarity	NPD3890	Phase 2
0.5882	Remote Similarity	NPD1896	Approved
0.5877	Remote Similarity	NPD3247	Clinical (unspecified phase)
0.5869	Remote Similarity	NPD6376	Discontinued
0.5865	Remote Similarity	NPD5854	Approved
0.5864	Remote Similarity	NPD3583	Phase 2
0.5864	Remote Similarity	NPD6579	Phase 2
0.5864	Remote Similarity	NPD6210	Phase 3
0.5859	Remote Similarity	NPD5146	Suspended
0.5859	Remote Similarity	NPD5473	Discontinued
0.5859	Remote Similarity	NPD8047	Clinical (unspecified phase)
0.5848	Remote Similarity	NPD6164	Phase 2
0.5848	Remote Similarity	NPD6165	Phase 2
0.5847	Remote Similarity	NPD175	Clinical (unspecified phase)
0.5842	Remote Similarity	NPD3486	Clinical (unspecified phase)
0.5841	Remote Similarity	NPD3968	Approved
0.5841	Remote Similarity	NPD5510	Approved
0.5837	Remote Similarity	NPD4854	Phase 3
0.5826	Remote Similarity	NPD3353	Approved
0.5825	Remote Similarity	NPD7406	Phase 2
0.5816	Remote Similarity	NPD482	Approved
0.5813	Remote Similarity	NPD1250	Clinical (unspecified phase)
0.581	Remote Similarity	NPD5017	Discontinued
0.581	Remote Similarity	NPD7903	Clinical (unspecified phase)
0.581	Remote Similarity	NPD200	Phase 2
0.581	Remote Similarity	NPD201	Phase 2
0.5806	Remote Similarity	NPD2363	Discontinued
0.5802	Remote Similarity	NPD4299	Phase 1
0.5799	Remote Similarity	NPD2787	Clinical (unspecified phase)
0.5797	Remote Similarity	NPD7027	Phase 3
0.5797	Remote Similarity	NPD1871	Approved
0.5792	Remote Similarity	NPD7026	Phase 2
0.5787	Remote Similarity	NPD4385	Clinical (unspecified phase)
0.5787	Remote Similarity	NPD4075	Phase 2
0.5787	Remote Similarity	NPD749	Clinical (unspecified phase)
0.5787	Remote Similarity	NPD272	Approved
0.5785	Remote Similarity	NPD7717	Approved
0.5785	Remote Similarity	NPD7716	Approved
0.5782	Remote Similarity	NPD6268	Phase 1
0.5782	Remote Similarity	NPD6269	Clinical (unspecified phase)
0.5779	Remote Similarity	NPD3989	Phase 3
0.5779	Remote Similarity	NPD3927	Phase 2
0.5775	Remote Similarity	NPD4559	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD1292	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD4541	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD6470	Phase 3
0.5773	Remote Similarity	NPD6578	Clinical (unspecified phase)
0.5767	Remote Similarity	NPD6855	Clinical (unspecified phase)
0.5754	Remote Similarity	NPD198	Clinical (unspecified phase)
0.575	Remote Similarity	NPD3990	Phase 3
0.5744	Remote Similarity	NPD1573	Approved
0.5744	Remote Similarity	NPD1575	Approved
0.5742	Remote Similarity	NPD2947	Clinical (unspecified phase)
0.5736	Remote Similarity	NPD4736	Clinical (unspecified phase)
0.5736	Remote Similarity	NPD4883	Approved
0.5728	Remote Similarity	NPD7207	Approved
0.5728	Remote Similarity	NPD7208	Approved
0.5728	Remote Similarity	NPD7209	Approved
0.5727	Remote Similarity	NPD8258	Clinical (unspecified phase)
0.5727	Remote Similarity	NPD1591	Approved
0.5727	Remote Similarity	NPD8257	Approved
0.5727	Remote Similarity	NPD8256	Approved
0.5722	Remote Similarity	NPD438	Approved
0.5722	Remote Similarity	NPD439	Approved
0.5721	Remote Similarity	NPD7401	Clinical (unspecified phase)
0.5721	Remote Similarity	NPD6521	Phase 3
0.5721	Remote Similarity	NPD7023	Clinical (unspecified phase)
0.5721	Remote Similarity	NPD6459	Phase 2
0.5721	Remote Similarity	NPD5728	Clinical (unspecified phase)
0.5721	Remote Similarity	NPD6520	Phase 3
0.5714	Remote Similarity	NPD7621	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD9599	Approved
0.5714	Remote Similarity	NPD7072	Phase 2
0.5714	Remote Similarity	NPD6827	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD6828	Phase 2
0.5708	Remote Similarity	NPD2881	Approved
0.5708	Remote Similarity	NPD2879	Approved
0.5707	Remote Similarity	NPD1630	Approved
0.5701	Remote Similarity	NPD7568	Phase 1
0.57	Remote Similarity	NPD2004	Clinical (unspecified phase)
0.57	Remote Similarity	NPD4348	Clinical (unspecified phase)
0.57	Remote Similarity	NPD5274	Clinical (unspecified phase)
0.57	Remote Similarity	NPD1291	Clinical (unspecified phase)
0.5699	Remote Similarity	NPD5138	Approved
0.5699	Remote Similarity	NPD5140	Approved
0.5693	Remote Similarity	NPD7564	Discontinued
0.5692	Remote Similarity	NPD2844	Phase 3
0.5686	Remote Similarity	NPD4988	Discontinued
0.5686	Remote Similarity	NPD3961	Discontinued
0.5683	Remote Similarity	NPD1722	Approved
0.5681	Remote Similarity	NPD6176	Phase 1
0.5678	Remote Similarity	NPD7065	Clinical (unspecified phase)
0.5678	Remote Similarity	NPD4181	Approved
0.5673	Remote Similarity	NPD8641	Approved
0.5672	Remote Similarity	NPD1895	Discontinued
0.5668	Remote Similarity	NPD7998	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD7204	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD4704	Discontinued
0.5662	Remote Similarity	NPD2823	Clinical (unspecified phase)
0.5659	Remote Similarity	NPD786	Approved
0.5657	Remote Similarity	NPD7662	Clinical (unspecified phase)
0.5657	Remote Similarity	NPD4128	Approved
0.5657	Remote Similarity	NPD3522	Approved
0.5654	Remote Similarity	NPD8115	Approved
0.5654	Remote Similarity	NPD6229	Phase 2
0.5654	Remote Similarity	NPD8114	Approved
0.5648	Remote Similarity	NPD6771	Discontinued
0.5644	Remote Similarity	NPD2094	Phase 2
0.5644	Remote Similarity	NPD2092	Phase 2
0.5644	Remote Similarity	NPD2095	Phase 2
0.5641	Remote Similarity	NPD1248	Discontinued
0.5638	Remote Similarity	NPD971	Clinical (unspecified phase)
0.5637	Remote Similarity	NPD4940	Approved
0.5636	Remote Similarity	NPD4395	Phase 1
0.5636	Remote Similarity	NPD3757	Clinical (unspecified phase)
0.5635	Remote Similarity	NPD1262	Discovery

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data