NPASS Compound

Structure

NPC471366 OpenBabel07101719522D 38 40 0 0 1 0 0 0 0 0999 V2000 6.7654 1.0563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2065 3.9831 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7897 2.7461 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5167 3.0075 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7078 -0.4071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7024 -0.5588 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0201 -2.4788 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3507 1.9012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 -1.3828 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7897 1.0563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3616 4.4709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3263 1.9012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8385 1.0563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0180 -0.4071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 2.5197 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0180 2.5197 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3019 1.9012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5167 3.9831 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.8629 0.0807 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0039 0.3691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9744 -2.2759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1731 3.0075 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3282 1.5441 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0180 1.5441 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1731 0.0807 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3282 4.4709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3968 0.8913 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9703 0.1020 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8629 1.0563 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1731 1.0563 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9582 0.5719 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6272 -3.0009 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 5.4465 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 -0.4071 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3511 1.0941 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2759 -1.3481 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1731 3.9831 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 1 10 2 0 0 0 0 2 11 1 0 0 0 0 3 17 2 0 0 0 0 4 18 1 0 0 0 0 5 19 1 0 0 0 0 6 20 1 0 0 0 0 7 21 1 0 0 0 0 9 34 1 0 0 0 0 10 17 1 0 0 0 0 11 18 1 0 0 0 0 12 13 1 0 0 0 0 12 17 1 0 0 0 0 13 29 1 0 0 0 0 14 19 1 0 0 0 0 14 25 1 0 0 0 0 15 22 1 0 0 0 0 15 23 2 0 0 0 0 16 22 1 0 0 0 0 16 24 1 0 0 0 0 18 26 1 0 0 0 0 19 29 1 1 0 0 0 20 31 2 0 0 0 0 20 35 1 0 0 0 0 21 32 2 0 0 0 0 21 36 1 0 0 0 0 22 37 1 1 0 0 0 23 27 1 0 0 0 0 24 29 1 6 0 0 0 24 30 1 0 0 0 0 25 30 1 1 0 0 0 25 34 1 0 0 0 0 26 33 2 0 0 0 0 26 37 1 0 0 0 0 27 35 1 1 0 0 0 27 38 1 0 0 0 0 28 30 1 6 0 0 0 28 36 1 0 0 0 0 28 38 1 0 0 0 0 29 8 1 6 0 0 0 30 23 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	532.3
Volume:	556.27
LogP:	4.214
LogD:	3.39
LogS:	-4.582
# Rotatable Bonds:	13
TPSA:	97.36
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.162
Synthetic Accessibility Score:	5.839
Fsp3:	0.7
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.695
MDCK Permeability:	5.3029536502435803e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.188

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.157
Plasma Protein Binding (PPB):	70.95352935791016%
Volume Distribution (VD):	2.299
Pgp-substrate:	35.778072357177734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.023
CYP1A2-substrate:	0.074
CYP2C19-inhibitor:	0.019
CYP2C19-substrate:	0.572
CYP2C9-inhibitor:	0.087
CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.115
CYP3A4-inhibitor:	0.649
CYP3A4-substrate:	0.457

ADMET: Excretion

Clearance (CL):	4.076
Half-life (T1/2):	0.054

ADMET: Toxicity

hERG Blockers:	0.134
Human Hepatotoxicity (H-HT):	0.932
Drug-inuced Liver Injury (DILI):	0.947
AMES Toxicity:	0.708
Rat Oral Acute Toxicity:	0.788
Maximum Recommended Daily Dose:	0.91
Skin Sensitization:	0.863
Carcinogencity:	0.289
Eye Corrosion:	0.011
Eye Irritation:	0.018
Respiratory Toxicity:	0.969

Download Data

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

Natural Product: NPC471366

Natural Product ID:	NPC471366
*Common Name:**	Rel-(2S,5R,6R,8S,9S,10R,18S,19S)-18,19-Diacetoxy-6-Methoxy-2-(2-Xi-Methylbutanoyloxy)Cleroda-3,13(16),14-Trien-18,19-Oxolane
IUPAC Name:	[(1S,3S,5S,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-methoxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 2-methylbutanoate
Synonyms:
Standard InCHIKey:	PRXYABXGJNKXKE-PKSUEKOCSA-N
Standard InCHI:	InChI=1S/C30H44O8/c1-10-17(3)12-13-29(8)19(5)14-25(34-9)30-23(27(35-20(6)31)38-28(30)36-21(7)32)15-22(16-24(29)30)37-26(33)18(4)11-2/h10,15,18-19,22,24-25,27-28H,1,3,11-14,16H2,2,4-9H3/t18?,19-,22+,24+,25+,27+,28+,29-,30-/m0/s1
SMILES:	CCC(C)C(=O)OC1CC2C(C(CC(C23C(OC(C3=C1)OC(=O)C)OC(=O)C)OC)C)(C)CCC(=C)C=C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2419875
PubChem CID:	73355249
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

*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
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	leaves and twigs	n.a.	n.a.	PMID[24033131]
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	twigs	n.a.	n.a.	PMID[25286284]
NPO32459	casearia balansae	Species	Salicaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[26699618]

☑ 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	5

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1374	Cell Line	WI-38	Homo sapiens	IC50	=	13300.0	nM	PMID[545308]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	7900.0	nM	PMID[545308]
NPT146	Cell Line	SK-OV-3	Homo sapiens	IC50	=	7200.0	nM	PMID[545308]
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	4800.0	nM	PMID[545308]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	5600.0	nM	PMID[545308]

☑ 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 NPC471366 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	217
0.1-0.2	1181
0.2-0.3	4335
0.3-0.4	9098
0.4-0.5	12785
0.5-0.6	7471
0.6-0.7	6227
0.7-0.8	1248
0.8-0.85	38
0.85-0.9	28
0.9-0.95	42
0.95-1	27

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC472186
1.0	High Similarity	NPC318917
1.0	High Similarity	NPC476800
0.9891	High Similarity	NPC472187
0.9891	High Similarity	NPC473204
0.9891	High Similarity	NPC473545
0.989	High Similarity	NPC472188
0.978	High Similarity	NPC171598
0.967	High Similarity	NPC472189
0.967	High Similarity	NPC471372
0.967	High Similarity	NPC471362
0.9579	High Similarity	NPC7613
0.9579	High Similarity	NPC7644
0.9579	High Similarity	NPC475889
0.9579	High Similarity	NPC127933
0.9479	High Similarity	NPC201880
0.9479	High Similarity	NPC81567
0.9479	High Similarity	NPC264867
0.9479	High Similarity	NPC470321
0.9479	High Similarity	NPC473207
0.9474	High Similarity	NPC471363
0.9474	High Similarity	NPC238397
0.9375	High Similarity	NPC134270
0.9348	High Similarity	NPC88507
0.9286	High Similarity	NPC184512
0.9286	High Similarity	NPC125423
0.9286	High Similarity	NPC88013
0.9192	High Similarity	NPC128795
0.9192	High Similarity	NPC135015
0.9192	High Similarity	NPC48548
0.9192	High Similarity	NPC217921
0.9192	High Similarity	NPC311223
0.9184	High Similarity	NPC252296
0.9149	High Similarity	NPC311166
0.91	High Similarity	NPC40728
0.91	High Similarity	NPC316974
0.901	High Similarity	NPC119550
0.8947	High Similarity	NPC94905
0.8947	High Similarity	NPC8954
0.89	High Similarity	NPC109376
0.8812	High Similarity	NPC470024
0.8812	High Similarity	NPC224660
0.88	High Similarity	NPC172867
0.88	High Similarity	NPC218158
0.8788	High Similarity	NPC132395
0.8788	High Similarity	NPC471364
0.8788	High Similarity	NPC471365
0.866	High Similarity	NPC98112
0.8641	High Similarity	NPC316708
0.8602	High Similarity	NPC69713
0.8558	High Similarity	NPC17791
0.8558	High Similarity	NPC470026
0.8495	Intermediate Similarity	NPC102640
0.8485	Intermediate Similarity	NPC477968
0.8485	Intermediate Similarity	NPC219285
0.8485	Intermediate Similarity	NPC228251
0.8485	Intermediate Similarity	NPC161527
0.8485	Intermediate Similarity	NPC477972
0.8485	Intermediate Similarity	NPC477971
0.8485	Intermediate Similarity	NPC20113
0.8476	Intermediate Similarity	NPC470025
0.8476	Intermediate Similarity	NPC328074
0.8476	Intermediate Similarity	NPC317460
0.8476	Intermediate Similarity	NPC321272
0.8416	Intermediate Similarity	NPC120009
0.8396	Intermediate Similarity	NPC470027
0.8387	Intermediate Similarity	NPC102996
0.837	Intermediate Similarity	NPC471367
0.8365	Intermediate Similarity	NPC112457
0.8316	Intermediate Similarity	NPC293044
0.8316	Intermediate Similarity	NPC470819
0.8229	Intermediate Similarity	NPC471370
0.8229	Intermediate Similarity	NPC471371
0.8229	Intermediate Similarity	NPC470817
0.8211	Intermediate Similarity	NPC477128
0.82	Intermediate Similarity	NPC473154
0.8191	Intermediate Similarity	NPC471368
0.8191	Intermediate Similarity	NPC471369
0.8173	Intermediate Similarity	NPC293512
0.8155	Intermediate Similarity	NPC222161
0.8144	Intermediate Similarity	NPC477574
0.8144	Intermediate Similarity	NPC474631
0.8119	Intermediate Similarity	NPC470761
0.8119	Intermediate Similarity	NPC473219
0.81	Intermediate Similarity	NPC100912
0.8081	Intermediate Similarity	NPC100892
0.8081	Intermediate Similarity	NPC471786
0.8081	Intermediate Similarity	NPC477970
0.8081	Intermediate Similarity	NPC135224
0.8081	Intermediate Similarity	NPC37603
0.8081	Intermediate Similarity	NPC477969
0.8077	Intermediate Similarity	NPC82251
0.8077	Intermediate Similarity	NPC239961
0.8061	Intermediate Similarity	NPC99653
0.8056	Intermediate Similarity	NPC474410
0.8056	Intermediate Similarity	NPC157441
0.8056	Intermediate Similarity	NPC293658
0.8056	Intermediate Similarity	NPC264153
0.8041	Intermediate Similarity	NPC469403
0.8039	Intermediate Similarity	NPC280991
0.8039	Intermediate Similarity	NPC198992
0.8036	Intermediate Similarity	NPC204731
0.8021	Intermediate Similarity	NPC263079
0.802	Intermediate Similarity	NPC72647
0.802	Intermediate Similarity	NPC107806
0.802	Intermediate Similarity	NPC474440
0.8019	Intermediate Similarity	NPC206618
0.8018	Intermediate Similarity	NPC122971
0.8	Intermediate Similarity	NPC475380
0.8	Intermediate Similarity	NPC323209
0.8	Intermediate Similarity	NPC209297
0.8	Intermediate Similarity	NPC118266
0.8	Intermediate Similarity	NPC472390
0.8	Intermediate Similarity	NPC112654
0.8	Intermediate Similarity	NPC165632
0.8	Intermediate Similarity	NPC475074
0.8	Intermediate Similarity	NPC73858
0.7981	Intermediate Similarity	NPC470768
0.798	Intermediate Similarity	NPC140277
0.798	Intermediate Similarity	NPC477722
0.798	Intermediate Similarity	NPC477130
0.798	Intermediate Similarity	NPC477129
0.798	Intermediate Similarity	NPC189513
0.7963	Intermediate Similarity	NPC473125
0.7963	Intermediate Similarity	NPC194951
0.7963	Intermediate Similarity	NPC12046
0.7961	Intermediate Similarity	NPC472552
0.7959	Intermediate Similarity	NPC65513
0.7959	Intermediate Similarity	NPC124374
0.7944	Intermediate Similarity	NPC83005
0.7941	Intermediate Similarity	NPC324841
0.7938	Intermediate Similarity	NPC261320
0.7938	Intermediate Similarity	NPC246028
0.7935	Intermediate Similarity	NPC469802
0.7935	Intermediate Similarity	NPC473685
0.7928	Intermediate Similarity	NPC473828
0.7928	Intermediate Similarity	NPC473617
0.7925	Intermediate Similarity	NPC38948
0.7921	Intermediate Similarity	NPC475446
0.7921	Intermediate Similarity	NPC125551
0.7921	Intermediate Similarity	NPC309503
0.7921	Intermediate Similarity	NPC155319
0.7921	Intermediate Similarity	NPC96597
0.7921	Intermediate Similarity	NPC311241
0.7921	Intermediate Similarity	NPC91197
0.7921	Intermediate Similarity	NPC239547
0.7905	Intermediate Similarity	NPC470763
0.7905	Intermediate Similarity	NPC476762
0.7905	Intermediate Similarity	NPC476760
0.7905	Intermediate Similarity	NPC470767
0.7905	Intermediate Similarity	NPC476761
0.79	Intermediate Similarity	NPC286612
0.79	Intermediate Similarity	NPC230347
0.79	Intermediate Similarity	NPC275310
0.7895	Intermediate Similarity	NPC472442
0.7895	Intermediate Similarity	NPC41129
0.789	Intermediate Similarity	NPC44298
0.789	Intermediate Similarity	NPC311592
0.789	Intermediate Similarity	NPC75167
0.789	Intermediate Similarity	NPC473128
0.789	Intermediate Similarity	NPC40133
0.789	Intermediate Similarity	NPC290608
0.789	Intermediate Similarity	NPC49413
0.7885	Intermediate Similarity	NPC471888
0.7885	Intermediate Similarity	NPC471885
0.7885	Intermediate Similarity	NPC471886
0.7885	Intermediate Similarity	NPC45897
0.7885	Intermediate Similarity	NPC471450
0.7885	Intermediate Similarity	NPC23584
0.7885	Intermediate Similarity	NPC254202
0.7885	Intermediate Similarity	NPC471887
0.7879	Intermediate Similarity	NPC163902
0.7879	Intermediate Similarity	NPC12297
0.7872	Intermediate Similarity	NPC472440
0.7864	Intermediate Similarity	NPC472554
0.7857	Intermediate Similarity	NPC48732
0.7857	Intermediate Similarity	NPC477071
0.7857	Intermediate Similarity	NPC220216
0.7857	Intermediate Similarity	NPC470914
0.7849	Intermediate Similarity	NPC25554
0.7843	Intermediate Similarity	NPC477928
0.7843	Intermediate Similarity	NPC216478
0.7838	Intermediate Similarity	NPC23046
0.7835	Intermediate Similarity	NPC106332
0.7835	Intermediate Similarity	NPC473879
0.7822	Intermediate Similarity	NPC194132
0.7822	Intermediate Similarity	NPC284194
0.7822	Intermediate Similarity	NPC211810
0.7822	Intermediate Similarity	NPC471765
0.7822	Intermediate Similarity	NPC221801
0.7818	Intermediate Similarity	NPC181145
0.781	Intermediate Similarity	NPC476763
0.781	Intermediate Similarity	NPC476764
0.78	Intermediate Similarity	NPC472360
0.78	Intermediate Similarity	NPC474841
0.78	Intermediate Similarity	NPC473434
0.78	Intermediate Similarity	NPC472416
0.78	Intermediate Similarity	NPC471446
0.7798	Intermediate Similarity	NPC222834
0.7788	Intermediate Similarity	NPC273005

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 NPC471366 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	178
0.1-0.2	1394
0.2-0.3	3885
0.3-0.4	2404
0.4-0.5	823
0.5-0.6	284
0.6-0.7	173
0.7-0.8	9
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
0.7593	Intermediate Similarity	NPD6686	Approved
0.75	Intermediate Similarity	NPD7638	Approved
0.7429	Intermediate Similarity	NPD7640	Approved
0.7429	Intermediate Similarity	NPD7639	Approved
0.7414	Intermediate Similarity	NPD7503	Approved
0.7304	Intermediate Similarity	NPD7327	Approved
0.7304	Intermediate Similarity	NPD7328	Approved
0.7265	Intermediate Similarity	NPD8515	Approved
0.7265	Intermediate Similarity	NPD8513	Phase 3
0.7265	Intermediate Similarity	NPD8516	Approved
0.7265	Intermediate Similarity	NPD8033	Approved
0.7265	Intermediate Similarity	NPD8517	Approved
0.7241	Intermediate Similarity	NPD7516	Approved
0.7179	Intermediate Similarity	NPD8294	Approved
0.7179	Intermediate Similarity	NPD8377	Approved
0.7172	Intermediate Similarity	NPD1694	Approved
0.717	Intermediate Similarity	NPD4225	Approved
0.7167	Intermediate Similarity	NPD7507	Approved
0.7119	Intermediate Similarity	NPD8335	Approved
0.7119	Intermediate Similarity	NPD8380	Approved
0.7119	Intermediate Similarity	NPD8379	Approved
0.7119	Intermediate Similarity	NPD8296	Approved
0.7119	Intermediate Similarity	NPD8378	Approved
0.7054	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD7319	Approved
0.6957	Remote Similarity	NPD8133	Approved
0.6944	Remote Similarity	NPD6648	Approved
0.6937	Remote Similarity	NPD6008	Approved
0.6923	Remote Similarity	NPD7637	Suspended
0.69	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6893	Remote Similarity	NPD6051	Approved
0.6875	Remote Similarity	NPD6412	Phase 2
0.687	Remote Similarity	NPD6882	Approved
0.6869	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6857	Remote Similarity	NPD5778	Approved
0.6857	Remote Similarity	NPD5779	Approved
0.6857	Remote Similarity	NPD6399	Phase 3
0.6852	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD7632	Discontinued
0.6792	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6792	Remote Similarity	NPD7900	Approved
0.678	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6777	Remote Similarity	NPD6370	Approved
0.6774	Remote Similarity	NPD7736	Approved
0.6754	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD5344	Discontinued
0.6721	Remote Similarity	NPD8328	Phase 3
0.6694	Remote Similarity	NPD8293	Discontinued
0.6694	Remote Similarity	NPD8074	Phase 3
0.6667	Remote Similarity	NPD8039	Approved
0.6667	Remote Similarity	NPD7492	Approved
0.6667	Remote Similarity	NPD7838	Discovery
0.6639	Remote Similarity	NPD7115	Discovery
0.6638	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6636	Remote Similarity	NPD7748	Approved
0.6613	Remote Similarity	NPD6616	Approved
0.6612	Remote Similarity	NPD6054	Approved
0.6606	Remote Similarity	NPD7902	Approved
0.6604	Remote Similarity	NPD6411	Approved
0.6602	Remote Similarity	NPD7334	Approved
0.6602	Remote Similarity	NPD6409	Approved
0.6602	Remote Similarity	NPD5330	Approved
0.6602	Remote Similarity	NPD7146	Approved
0.6602	Remote Similarity	NPD7521	Approved
0.6602	Remote Similarity	NPD6684	Approved
0.656	Remote Similarity	NPD7078	Approved
0.6522	Remote Similarity	NPD6899	Approved
0.6522	Remote Similarity	NPD6881	Approved
0.6509	Remote Similarity	NPD46	Approved
0.6509	Remote Similarity	NPD6698	Approved
0.65	Remote Similarity	NPD6009	Approved
0.6496	Remote Similarity	NPD6649	Approved
0.6496	Remote Similarity	NPD6650	Approved
0.6491	Remote Similarity	NPD5739	Approved
0.6491	Remote Similarity	NPD6675	Approved
0.6491	Remote Similarity	NPD7128	Approved
0.6491	Remote Similarity	NPD6402	Approved
0.6476	Remote Similarity	NPD6672	Approved
0.6476	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6476	Remote Similarity	NPD5737	Approved
0.6476	Remote Similarity	NPD6903	Approved
0.6475	Remote Similarity	NPD6059	Approved
0.6466	Remote Similarity	NPD6372	Approved
0.6466	Remote Similarity	NPD6373	Approved
0.6452	Remote Similarity	NPD6067	Discontinued
0.6449	Remote Similarity	NPD7515	Phase 2
0.6441	Remote Similarity	NPD6053	Discontinued
0.6441	Remote Similarity	NPD8297	Approved
0.6435	Remote Similarity	NPD5697	Approved
0.6423	Remote Similarity	NPD6016	Approved
0.6423	Remote Similarity	NPD6015	Approved
0.6422	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6415	Remote Similarity	NPD6101	Approved
0.6415	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.641	Remote Similarity	NPD7290	Approved
0.641	Remote Similarity	NPD7102	Approved
0.641	Remote Similarity	NPD6883	Approved
0.6408	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6381	Remote Similarity	NPD4250	Approved
0.6381	Remote Similarity	NPD4251	Approved
0.6381	Remote Similarity	NPD3573	Approved
0.6379	Remote Similarity	NPD7320	Approved
0.6379	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6371	Remote Similarity	NPD5988	Approved
0.6356	Remote Similarity	NPD6847	Approved
0.6356	Remote Similarity	NPD8130	Phase 1
0.6356	Remote Similarity	NPD6869	Approved
0.6356	Remote Similarity	NPD6617	Approved
0.6341	Remote Similarity	NPD6319	Approved
0.6325	Remote Similarity	NPD6014	Approved
0.6325	Remote Similarity	NPD6013	Approved
0.6325	Remote Similarity	NPD6012	Approved
0.6311	Remote Similarity	NPD6695	Phase 3
0.6304	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.6296	Remote Similarity	NPD8035	Phase 2
0.6296	Remote Similarity	NPD5693	Phase 1
0.6296	Remote Similarity	NPD7983	Approved
0.6296	Remote Similarity	NPD8034	Phase 2
0.6293	Remote Similarity	NPD5701	Approved
0.6286	Remote Similarity	NPD4249	Approved
0.6262	Remote Similarity	NPD1695	Approved
0.625	Remote Similarity	NPD4632	Approved
0.625	Remote Similarity	NPD4786	Approved
0.625	Remote Similarity	NPD3668	Phase 3
0.6239	Remote Similarity	NPD6011	Approved
0.6238	Remote Similarity	NPD7645	Phase 2
0.6231	Remote Similarity	NPD7260	Phase 2
0.6216	Remote Similarity	NPD7839	Suspended
0.6214	Remote Similarity	NPD5209	Approved
0.6214	Remote Similarity	NPD3667	Approved
0.6204	Remote Similarity	NPD5207	Approved
0.6176	Remote Similarity	NPD7525	Registered
0.6176	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD8264	Approved
0.6161	Remote Similarity	NPD6084	Phase 2
0.6161	Remote Similarity	NPD6083	Phase 2
0.6154	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6147	Remote Similarity	NPD6050	Approved
0.6147	Remote Similarity	NPD6079	Approved
0.6147	Remote Similarity	NPD5694	Approved
0.6132	Remote Similarity	NPD6098	Approved
0.6132	Remote Similarity	NPD3618	Phase 1
0.6126	Remote Similarity	NPD5695	Phase 3
0.6126	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD6673	Approved
0.6111	Remote Similarity	NPD6080	Approved
0.6111	Remote Similarity	NPD5328	Approved
0.6111	Remote Similarity	NPD6904	Approved
0.6087	Remote Similarity	NPD5211	Phase 2
0.6083	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6078	Remote Similarity	NPD6929	Approved
0.6075	Remote Similarity	NPD7750	Discontinued
0.6075	Remote Similarity	NPD7524	Approved
0.6063	Remote Similarity	NPD7604	Phase 2
0.6055	Remote Similarity	NPD3168	Discontinued
0.6055	Remote Similarity	NPD5692	Phase 3
0.6053	Remote Similarity	NPD5285	Approved
0.6053	Remote Similarity	NPD5286	Approved
0.6053	Remote Similarity	NPD4696	Approved
0.6038	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6038	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6038	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6036	Remote Similarity	NPD5282	Discontinued
0.6036	Remote Similarity	NPD6001	Approved
0.6032	Remote Similarity	NPD5983	Phase 2
0.6019	Remote Similarity	NPD4819	Approved
0.6019	Remote Similarity	NPD7332	Phase 2
0.6019	Remote Similarity	NPD6931	Approved
0.6019	Remote Similarity	NPD4820	Approved
0.6019	Remote Similarity	NPD6930	Phase 2
0.6019	Remote Similarity	NPD7514	Phase 3
0.6019	Remote Similarity	NPD4822	Approved
0.6019	Remote Similarity	NPD4821	Approved
0.6018	Remote Similarity	NPD4755	Approved
0.6	Remote Similarity	NPD7101	Approved
0.6	Remote Similarity	NPD7100	Approved
0.6	Remote Similarity	NPD3669	Approved
0.6	Remote Similarity	NPD6033	Approved
0.6	Remote Similarity	NPD6371	Approved
0.6	Remote Similarity	NPD5284	Approved
0.6	Remote Similarity	NPD6942	Approved
0.6	Remote Similarity	NPD7154	Phase 3
0.6	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6	Remote Similarity	NPD7339	Approved
0.6	Remote Similarity	NPD5281	Approved
0.5983	Remote Similarity	NPD5141	Approved
0.598	Remote Similarity	NPD7145	Approved
0.598	Remote Similarity	NPD4271	Approved
0.598	Remote Similarity	NPD4268	Approved
0.5969	Remote Similarity	NPD8451	Approved
0.5969	Remote Similarity	NPD6336	Discontinued
0.5965	Remote Similarity	NPD5696	Approved
0.5962	Remote Similarity	NPD6902	Approved
0.5948	Remote Similarity	NPD4633	Approved
0.5948	Remote Similarity	NPD5226	Approved
0.5948	Remote Similarity	NPD5225	Approved
0.5948	Remote Similarity	NPD5224	Approved
0.5946	Remote Similarity	NPD4202	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