NPASS Compound

Structure

CID283409 OpenBabel06191716092D 31 33 0 0 1 0 0 0 0 0999 V2000 -5.5574 -0.8622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0257 -0.0436 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9635 1.5463 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2625 -2.4978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5261 -2.3471 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3760 -4.3661 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9727 -1.1832 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5718 0.6718 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4957 -0.8925 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0552 -0.0290 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5424 0.6718 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3495 -1.5311 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7325 -2.9057 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3760 -3.3956 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9667 -0.0870 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1143 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7648 -1.5311 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1827 -1.0333 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1476 -0.0870 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0571 -1.4544 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5825 0.8187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3815 -0.8925 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9316 -1.0333 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8195 -3.8724 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4645 -2.9103 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0804 1.6519 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3277 -1.1085 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8518 -2.4978 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0571 -2.4250 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6121 0.8332 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 10 1 0 0 0 0 4 12 2 0 0 0 0 5 13 1 0 0 0 0 6 14 1 0 0 0 0 8 11 1 0 0 0 0 9 16 1 0 0 0 0 9 17 1 0 0 0 0 10 21 1 0 0 0 0 11 3 1 6 0 0 0 11 19 1 0 0 0 0 12 22 1 0 0 0 0 13 24 2 0 0 0 0 13 28 1 0 0 0 0 14 25 2 0 0 0 0 14 29 1 0 0 0 0 15 8 1 6 0 0 0 15 18 1 0 0 0 0 15 30 1 0 0 0 0 16 19 1 0 0 0 0 16 31 1 6 0 0 0 17 23 1 6 0 0 0 17 28 1 0 0 0 0 18 12 1 1 0 0 0 18 20 1 0 0 0 0 19 23 1 1 0 0 0 20 23 1 6 0 0 0 20 29 1 0 0 0 0 21 26 2 0 0 0 0 21 31 1 0 0 0 0 22 27 2 0 0 0 0 22 30 1 0 0 0 0 23 7 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	436.21
Volume:	437.834
LogP:	2.906
LogD:	2.661
LogS:	-3.35
# Rotatable Bonds:	7
TPSA:	105.2
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.376
Synthetic Accessibility Score:	4.771
Fsp3:	0.739
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.993
MDCK Permeability:	0.00011758794425986707
Pgp-inhibitor:	0.999
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.012
20% Bioavailability (F20%):	0.888
30% Bioavailability (F30%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.607
Plasma Protein Binding (PPB):	42.0128059387207%
Volume Distribution (VD):	1.358
Pgp-substrate:	40.054691314697266%

ADMET: Metabolism

CYP1A2-inhibitor:	0.043
CYP1A2-substrate:	0.034
CYP2C19-inhibitor:	0.017
CYP2C19-substrate:	0.387
CYP2C9-inhibitor:	0.058
CYP2C9-substrate:	0.041
CYP2D6-inhibitor:	0.105
CYP2D6-substrate:	0.067
CYP3A4-inhibitor:	0.422
CYP3A4-substrate:	0.405

ADMET: Excretion

Clearance (CL):	4.88
Half-life (T1/2):	0.79

ADMET: Toxicity

hERG Blockers:	0.02
Human Hepatotoxicity (H-HT):	0.58
Drug-inuced Liver Injury (DILI):	0.938
AMES Toxicity:	0.027
Rat Oral Acute Toxicity:	0.562
Maximum Recommended Daily Dose:	0.013
Skin Sensitization:	0.657
Carcinogencity:	0.093
Eye Corrosion:	0.152
Eye Irritation:	0.133
Respiratory Toxicity:	0.938

Download Data

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

Natural Product: NPC283409

Natural Product ID:	NPC283409
*Common Name:**	Athrolide A
IUPAC Name:	[(3aS,5R,5aS,6S,8R,8aS,9S,9aR)-8,9-diacetyloxy-5,8a-dimethyl-1-methylidene-2-oxo-4,5,5a,6,7,8,9,9a-octahydro-3aH-azuleno[6,5-b]furan-6-yl] 2-methylpropanoate
Synonyms:	Athrolide A
Standard InCHIKey:	NDMSWUKPDPLPAZ-WDPXAWCQSA-N
Standard InCHI:	InChI=1S/C23H32O8/c1-10(2)21(26)31-16-9-17(28-13(5)24)23(7)19(16)11(3)8-15-18(12(4)22(27)30-15)20(23)29-14(6)25/h10-11,15-20H,4,8-9H2,1-3,5-7H3/t11-,15+,16+,17-,18-,19-,20+,23-/m1/s1
SMILES:	CC(C)C(=O)O[C@H]1C[C@H]([C@]2(C)[C@@H]1[C@H](C)C[C@H]1[C@@H](C(=C)C(=O)O1)[C@@H]2OC(=O)C)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1834671
PubChem CID:	56599133
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001543] Sesquiterpene lactones

*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
NPO22099	Athroisma proteiforme	Species	Asteraceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21995542]
NPO22099	Athroisma proteiforme	Species	Asteraceae	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	3
Others	1

Activity Type	# Activity
Cell Line	1
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell Line	A2780	Homo sapiens	IC50	=	2100.0	nM	PMID[495828]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	34300.0	nM	PMID[495828]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	32700.0	nM	PMID[495828]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Ratio IC50	=	1.0	n.a.	PMID[495828]

☑ 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 NPC283409 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	277
0.1-0.2	2141
0.2-0.3	7564
0.3-0.4	15455
0.4-0.5	8390
0.5-0.6	6448
0.6-0.7	2037
0.7-0.8	279
0.8-0.85	46
0.85-0.9	34
0.9-0.95	23
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.988	High Similarity	NPC471149
0.9759	High Similarity	NPC24728
0.931	High Similarity	NPC57304
0.931	High Similarity	NPC35959
0.931	High Similarity	NPC63193
0.931	High Similarity	NPC133888
0.931	High Similarity	NPC171360
0.931	High Similarity	NPC29821
0.931	High Similarity	NPC293001
0.9195	High Similarity	NPC297474
0.9195	High Similarity	NPC54065
0.9195	High Similarity	NPC35809
0.9176	High Similarity	NPC304558
0.9157	High Similarity	NPC246076
0.9091	High Similarity	NPC286341
0.9091	High Similarity	NPC191339
0.908	High Similarity	NPC472872
0.908	High Similarity	NPC155935
0.8901	High Similarity	NPC24956
0.8901	High Similarity	NPC18019
0.8764	High Similarity	NPC216284
0.875	High Similarity	NPC207114
0.875	High Similarity	NPC217983
0.875	High Similarity	NPC79549
0.8736	High Similarity	NPC64153
0.8736	High Similarity	NPC56593
0.8696	High Similarity	NPC91771
0.8696	High Similarity	NPC142529
0.8667	High Similarity	NPC155215
0.8652	High Similarity	NPC215556
0.8605	High Similarity	NPC54468
0.8587	High Similarity	NPC476053
0.8587	High Similarity	NPC472873
0.8587	High Similarity	NPC167893
0.8571	High Similarity	NPC473263
0.8571	High Similarity	NPC258216
0.8571	High Similarity	NPC472874
0.8571	High Similarity	NPC473234
0.8571	High Similarity	NPC308656
0.8571	High Similarity	NPC60386
0.8571	High Similarity	NPC473273
0.8556	High Similarity	NPC19087
0.8523	High Similarity	NPC238593
0.8523	High Similarity	NPC187661
0.8478	Intermediate Similarity	NPC127019
0.8462	Intermediate Similarity	NPC184063
0.8444	Intermediate Similarity	NPC38392
0.8427	Intermediate Similarity	NPC270270
0.8409	Intermediate Similarity	NPC300082
0.8409	Intermediate Similarity	NPC284534
0.8409	Intermediate Similarity	NPC235792
0.8409	Intermediate Similarity	NPC204105
0.8404	Intermediate Similarity	NPC471150
0.8404	Intermediate Similarity	NPC311904
0.8387	Intermediate Similarity	NPC163228
0.8387	Intermediate Similarity	NPC213698
0.8372	Intermediate Similarity	NPC47635
0.837	Intermediate Similarity	NPC153590
0.837	Intermediate Similarity	NPC200237
0.8333	Intermediate Similarity	NPC171759
0.8333	Intermediate Similarity	NPC224652
0.8298	Intermediate Similarity	NPC213078
0.8295	Intermediate Similarity	NPC224386
0.8295	Intermediate Similarity	NPC194859
0.828	Intermediate Similarity	NPC473331
0.8261	Intermediate Similarity	NPC475925
0.8256	Intermediate Similarity	NPC293418
0.8256	Intermediate Similarity	NPC73052
0.8256	Intermediate Similarity	NPC290508
0.8256	Intermediate Similarity	NPC6823
0.8229	Intermediate Similarity	NPC186861
0.8222	Intermediate Similarity	NPC118601
0.8222	Intermediate Similarity	NPC201658
0.8211	Intermediate Similarity	NPC108475
0.8211	Intermediate Similarity	NPC170143
0.8211	Intermediate Similarity	NPC213947
0.8211	Intermediate Similarity	NPC161493
0.8193	Intermediate Similarity	NPC143979
0.8193	Intermediate Similarity	NPC320537
0.8191	Intermediate Similarity	NPC170120
0.8191	Intermediate Similarity	NPC67584
0.8182	Intermediate Similarity	NPC128246
0.8182	Intermediate Similarity	NPC111409
0.8182	Intermediate Similarity	NPC245665
0.8132	Intermediate Similarity	NPC178875
0.8125	Intermediate Similarity	NPC45125
0.8085	Intermediate Similarity	NPC198853
0.8065	Intermediate Similarity	NPC221282
0.8065	Intermediate Similarity	NPC133698
0.8043	Intermediate Similarity	NPC168679
0.8043	Intermediate Similarity	NPC4986
0.8043	Intermediate Similarity	NPC12872
0.8041	Intermediate Similarity	NPC471381
0.8021	Intermediate Similarity	NPC181151
0.8021	Intermediate Similarity	NPC474313
0.8	Intermediate Similarity	NPC52044
0.8	Intermediate Similarity	NPC224689
0.798	Intermediate Similarity	NPC473148
0.7955	Intermediate Similarity	NPC126248
0.7938	Intermediate Similarity	NPC249171
0.7938	Intermediate Similarity	NPC221615
0.7938	Intermediate Similarity	NPC49833
0.7917	Intermediate Similarity	NPC126156
0.7912	Intermediate Similarity	NPC236692
0.7912	Intermediate Similarity	NPC67493
0.7912	Intermediate Similarity	NPC309757
0.7907	Intermediate Similarity	NPC208223
0.7905	Intermediate Similarity	NPC471382
0.7895	Intermediate Similarity	NPC470010
0.7895	Intermediate Similarity	NPC262133
0.7895	Intermediate Similarity	NPC477131
0.7895	Intermediate Similarity	NPC470013
0.7895	Intermediate Similarity	NPC281775
0.7895	Intermediate Similarity	NPC323008
0.7872	Intermediate Similarity	NPC131209
0.7841	Intermediate Similarity	NPC258965
0.7841	Intermediate Similarity	NPC156658
0.7835	Intermediate Similarity	NPC304445
0.7835	Intermediate Similarity	NPC236580
0.7822	Intermediate Similarity	NPC291643
0.7822	Intermediate Similarity	NPC54737
0.78	Intermediate Similarity	NPC221421
0.7778	Intermediate Similarity	NPC471767
0.7778	Intermediate Similarity	NPC128429
0.7778	Intermediate Similarity	NPC150923
0.7767	Intermediate Similarity	NPC59489
0.7767	Intermediate Similarity	NPC139838
0.7766	Intermediate Similarity	NPC475776
0.7766	Intermediate Similarity	NPC37607
0.7766	Intermediate Similarity	NPC301969
0.7757	Intermediate Similarity	NPC36754
0.7755	Intermediate Similarity	NPC470188
0.7745	Intermediate Similarity	NPC470192
0.7745	Intermediate Similarity	NPC26617
0.7742	Intermediate Similarity	NPC91248
0.7736	Intermediate Similarity	NPC471380
0.7732	Intermediate Similarity	NPC113433
0.7727	Intermediate Similarity	NPC182550
0.7717	Intermediate Similarity	NPC162071
0.7717	Intermediate Similarity	NPC470242
0.7717	Intermediate Similarity	NPC107787
0.7711	Intermediate Similarity	NPC5714
0.77	Intermediate Similarity	NPC78127
0.77	Intermediate Similarity	NPC250594
0.77	Intermediate Similarity	NPC471757
0.77	Intermediate Similarity	NPC105725
0.77	Intermediate Similarity	NPC80144
0.7692	Intermediate Similarity	NPC471884
0.7692	Intermediate Similarity	NPC115786
0.7692	Intermediate Similarity	NPC156485
0.7685	Intermediate Similarity	NPC161060
0.7684	Intermediate Similarity	NPC74103
0.7684	Intermediate Similarity	NPC123177
0.7684	Intermediate Similarity	NPC150978
0.7684	Intermediate Similarity	NPC290651
0.7684	Intermediate Similarity	NPC70595
0.766	Intermediate Similarity	NPC92974
0.7653	Intermediate Similarity	NPC58267
0.7653	Intermediate Similarity	NPC263674
0.7653	Intermediate Similarity	NPC261372
0.7647	Intermediate Similarity	NPC44004
0.764	Intermediate Similarity	NPC474981
0.764	Intermediate Similarity	NPC276356
0.764	Intermediate Similarity	NPC74673
0.764	Intermediate Similarity	NPC69271
0.7634	Intermediate Similarity	NPC175293
0.7634	Intermediate Similarity	NPC190753
0.7629	Intermediate Similarity	NPC280877
0.7629	Intermediate Similarity	NPC304886
0.7629	Intermediate Similarity	NPC475900
0.7609	Intermediate Similarity	NPC78089
0.7604	Intermediate Similarity	NPC470187
0.7604	Intermediate Similarity	NPC475788
0.7604	Intermediate Similarity	NPC475700
0.7604	Intermediate Similarity	NPC135776
0.76	Intermediate Similarity	NPC67296
0.7582	Intermediate Similarity	NPC215294
0.7582	Intermediate Similarity	NPC257358
0.7582	Intermediate Similarity	NPC474472
0.7579	Intermediate Similarity	NPC475748
0.7579	Intermediate Similarity	NPC253144
0.7556	Intermediate Similarity	NPC281949
0.7556	Intermediate Similarity	NPC301477
0.7556	Intermediate Similarity	NPC25684
0.7553	Intermediate Similarity	NPC177629
0.7553	Intermediate Similarity	NPC58219
0.7551	Intermediate Similarity	NPC476009
0.7551	Intermediate Similarity	NPC474297
0.7528	Intermediate Similarity	NPC19841
0.7527	Intermediate Similarity	NPC476015
0.7527	Intermediate Similarity	NPC474045
0.7527	Intermediate Similarity	NPC50637
0.7527	Intermediate Similarity	NPC474762
0.7527	Intermediate Similarity	NPC469676
0.7527	Intermediate Similarity	NPC261253
0.7526	Intermediate Similarity	NPC471446
0.7526	Intermediate Similarity	NPC473434
0.7526	Intermediate Similarity	NPC474841
0.7525	Intermediate Similarity	NPC49393
0.75	Intermediate Similarity	NPC70865

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 NPC283409 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	314
0.1-0.2	2886
0.2-0.3	3880
0.3-0.4	1422
0.4-0.5	386
0.5-0.6	225
0.6-0.7	33
0.7-0.8	4
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
0.8043	Intermediate Similarity	NPD1695	Approved
0.7745	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7196	Intermediate Similarity	NPD6371	Approved
0.7083	Intermediate Similarity	NPD4251	Approved
0.7083	Intermediate Similarity	NPD4250	Approved
0.7041	Intermediate Similarity	NPD5785	Approved
0.6979	Remote Similarity	NPD4249	Approved
0.6909	Remote Similarity	NPD6053	Discontinued
0.6875	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6822	Remote Similarity	NPD6008	Approved
0.6737	Remote Similarity	NPD6435	Approved
0.6702	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6701	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.67	Remote Similarity	NPD6698	Approved
0.67	Remote Similarity	NPD46	Approved
0.6667	Remote Similarity	NPD6903	Approved
0.6667	Remote Similarity	NPD5362	Discontinued
0.6633	Remote Similarity	NPD5330	Approved
0.6633	Remote Similarity	NPD7521	Approved
0.6633	Remote Similarity	NPD7334	Approved
0.6633	Remote Similarity	NPD7146	Approved
0.6633	Remote Similarity	NPD6409	Approved
0.6633	Remote Similarity	NPD6684	Approved
0.6571	Remote Similarity	NPD7638	Approved
0.6562	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6545	Remote Similarity	NPD6686	Approved
0.6531	Remote Similarity	NPD1694	Approved
0.6531	Remote Similarity	NPD5363	Approved
0.6526	Remote Similarity	NPD4822	Approved
0.6526	Remote Similarity	NPD4819	Approved
0.6526	Remote Similarity	NPD4821	Approved
0.6526	Remote Similarity	NPD4820	Approved
0.6526	Remote Similarity	NPD5368	Approved
0.6509	Remote Similarity	NPD7639	Approved
0.6509	Remote Similarity	NPD7640	Approved
0.6505	Remote Similarity	NPD5282	Discontinued
0.65	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD7154	Phase 3
0.6489	Remote Similarity	NPD4271	Approved
0.6489	Remote Similarity	NPD4268	Approved
0.6458	Remote Similarity	NPD5369	Approved
0.6442	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD6399	Phase 3
0.6392	Remote Similarity	NPD4270	Approved
0.6392	Remote Similarity	NPD4269	Approved
0.6373	Remote Similarity	NPD7838	Discovery
0.6311	Remote Similarity	NPD8034	Phase 2
0.6311	Remote Similarity	NPD8035	Phase 2
0.6311	Remote Similarity	NPD5693	Phase 1
0.63	Remote Similarity	NPD5786	Approved
0.6261	Remote Similarity	NPD8133	Approved
0.623	Remote Similarity	NPD7507	Approved
0.6228	Remote Similarity	NPD6650	Approved
0.6228	Remote Similarity	NPD6649	Approved
0.6224	Remote Similarity	NPD5209	Approved
0.6214	Remote Similarity	NPD5207	Approved
0.6195	Remote Similarity	NPD6372	Approved
0.6195	Remote Similarity	NPD6373	Approved
0.6186	Remote Similarity	NPD4252	Approved
0.6176	Remote Similarity	NPD6672	Approved
0.6176	Remote Similarity	NPD5737	Approved
0.6168	Remote Similarity	NPD6084	Phase 2
0.6168	Remote Similarity	NPD6083	Phase 2
0.6162	Remote Similarity	NPD5331	Approved
0.6162	Remote Similarity	NPD5332	Approved
0.6161	Remote Similarity	NPD6412	Phase 2
0.6161	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6154	Remote Similarity	NPD7983	Approved
0.6146	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6132	Remote Similarity	NPD5695	Phase 3
0.6122	Remote Similarity	NPD4790	Discontinued
0.6117	Remote Similarity	NPD6673	Approved
0.6117	Remote Similarity	NPD6051	Approved
0.6117	Remote Similarity	NPD6080	Approved
0.6117	Remote Similarity	NPD6904	Approved
0.6111	Remote Similarity	NPD4225	Approved
0.6111	Remote Similarity	NPD5696	Approved
0.6106	Remote Similarity	NPD6899	Approved
0.6106	Remote Similarity	NPD6881	Approved
0.6106	Remote Similarity	NPD7320	Approved
0.6091	Remote Similarity	NPD7632	Discontinued
0.6087	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.608	Remote Similarity	NPD7319	Approved
0.6071	Remote Similarity	NPD5739	Approved
0.6071	Remote Similarity	NPD7128	Approved
0.6071	Remote Similarity	NPD6402	Approved
0.6071	Remote Similarity	NPD6675	Approved
0.6038	Remote Similarity	NPD6001	Approved
0.6034	Remote Similarity	NPD6882	Approved
0.6034	Remote Similarity	NPD8297	Approved
0.6033	Remote Similarity	NPD8033	Approved
0.6022	Remote Similarity	NPD5777	Approved
0.6018	Remote Similarity	NPD5697	Approved
0.6016	Remote Similarity	NPD7492	Approved
0.6	Remote Similarity	NPD7102	Approved
0.6	Remote Similarity	NPD7637	Suspended
0.6	Remote Similarity	NPD6050	Approved
0.6	Remote Similarity	NPD4788	Approved
0.6	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6	Remote Similarity	NPD7290	Approved
0.6	Remote Similarity	NPD6883	Approved
0.6	Remote Similarity	NPD8039	Approved
0.598	Remote Similarity	NPD6098	Approved
0.5979	Remote Similarity	NPD4802	Phase 2
0.5979	Remote Similarity	NPD4238	Approved
0.5968	Remote Similarity	NPD6616	Approved
0.5966	Remote Similarity	NPD7115	Discovery
0.5963	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.595	Remote Similarity	NPD6319	Approved
0.595	Remote Similarity	NPD6054	Approved
0.5948	Remote Similarity	NPD6847	Approved
0.5948	Remote Similarity	NPD8130	Phase 1
0.5948	Remote Similarity	NPD6617	Approved
0.5948	Remote Similarity	NPD6869	Approved
0.5943	Remote Similarity	NPD5778	Approved
0.5943	Remote Similarity	NPD5779	Approved
0.5938	Remote Similarity	NPD6845	Suspended
0.592	Remote Similarity	NPD7078	Approved
0.5917	Remote Similarity	NPD7327	Approved
0.5917	Remote Similarity	NPD7328	Approved
0.5913	Remote Similarity	NPD6014	Approved
0.5913	Remote Similarity	NPD6013	Approved
0.5913	Remote Similarity	NPD6012	Approved
0.5905	Remote Similarity	NPD5692	Phase 3
0.5893	Remote Similarity	NPD6052	Approved
0.5888	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5888	Remote Similarity	NPD7900	Approved
0.5882	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.5877	Remote Similarity	NPD5701	Approved
0.5873	Remote Similarity	NPD7736	Approved
0.587	Remote Similarity	NPD229	Approved
0.5868	Remote Similarity	NPD7516	Approved
0.5865	Remote Similarity	NPD5208	Approved
0.5862	Remote Similarity	NPD3198	Approved
0.5859	Remote Similarity	NPD7260	Phase 2
0.5854	Remote Similarity	NPD6370	Approved
0.5849	Remote Similarity	NPD5284	Approved
0.5849	Remote Similarity	NPD6411	Approved
0.5849	Remote Similarity	NPD5281	Approved
0.5849	Remote Similarity	NPD5694	Approved
0.5847	Remote Similarity	NPD4632	Approved
0.5841	Remote Similarity	NPD4056	Clinical (unspecified phase)
0.5841	Remote Similarity	NPD4057	Clinical (unspecified phase)
0.5826	Remote Similarity	NPD6011	Approved
0.5826	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.582	Remote Similarity	NPD6059	Approved
0.582	Remote Similarity	NPD8294	Approved
0.582	Remote Similarity	NPD8377	Approved
0.5794	Remote Similarity	NPD8293	Discontinued
0.5784	Remote Similarity	NPD3133	Approved
0.5784	Remote Similarity	NPD3665	Phase 1
0.5784	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5784	Remote Similarity	NPD3666	Approved
0.5776	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.5772	Remote Similarity	NPD6016	Approved
0.5772	Remote Similarity	NPD8378	Approved
0.5772	Remote Similarity	NPD8380	Approved
0.5772	Remote Similarity	NPD8296	Approved
0.5772	Remote Similarity	NPD7503	Approved
0.5772	Remote Similarity	NPD8335	Approved
0.5772	Remote Similarity	NPD6015	Approved
0.5772	Remote Similarity	NPD8379	Approved
0.5766	Remote Similarity	NPD6648	Approved
0.5739	Remote Similarity	NPD6685	Approved
0.5727	Remote Similarity	NPD7902	Approved
0.5726	Remote Similarity	NPD5988	Approved
0.5714	Remote Similarity	NPD1700	Approved
0.5714	Remote Similarity	NPD5344	Discontinued
0.5702	Remote Similarity	NPD6009	Approved
0.5688	Remote Similarity	NPD5210	Approved
0.5688	Remote Similarity	NPD4629	Approved
0.5686	Remote Similarity	NPD6695	Phase 3
0.568	Remote Similarity	NPD7604	Phase 2
0.5678	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.5664	Remote Similarity	NPD5211	Phase 2
0.566	Remote Similarity	NPD6101	Approved
0.566	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.566	Remote Similarity	NPD4753	Phase 2
0.5645	Remote Similarity	NPD8515	Approved
0.5645	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5645	Remote Similarity	NPD8513	Phase 3
0.5645	Remote Similarity	NPD8268	Approved
0.5645	Remote Similarity	NPD8269	Approved
0.5645	Remote Similarity	NPD8266	Approved
0.5645	Remote Similarity	NPD8516	Approved
0.5645	Remote Similarity	NPD5983	Phase 2
0.5645	Remote Similarity	NPD8267	Approved
0.5645	Remote Similarity	NPD8517	Approved
0.5636	Remote Similarity	NPD7839	Suspended
0.5631	Remote Similarity	NPD4786	Approved
0.5631	Remote Similarity	NPD3668	Phase 3
0.5625	Remote Similarity	NPD4696	Approved
0.5625	Remote Similarity	NPD5285	Approved
0.5625	Remote Similarity	NPD5286	Approved
0.562	Remote Similarity	NPD6274	Approved
0.561	Remote Similarity	NPD7101	Approved
0.561	Remote Similarity	NPD7100	Approved
0.5603	Remote Similarity	NPD6614	Approved

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