NPASS Compound

Structure

NPC471363 OpenBabel07101719522D 36 38 0 0 1 0 0 0 0 0999 V2000 6.7567 1.0549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2037 3.9780 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9544 0.5712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7823 2.7426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5160 3.0036 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7031 -0.4066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0188 -2.4756 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3464 1.8987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7823 1.0549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3599 4.4652 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0013 0.3686 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3208 1.8987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8336 1.0549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0154 -0.4066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3278 2.5165 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0154 2.5165 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2951 1.8987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5160 3.9780 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.8592 0.0806 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9719 -2.2730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1716 3.0036 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3278 1.5421 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0154 1.5421 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1716 0.0806 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3278 4.4652 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3963 0.8901 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9690 0.1018 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8592 1.0549 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1716 1.0549 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6238 -2.9971 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3278 -0.4066 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3278 5.4395 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3494 1.0927 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2730 -1.3463 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1716 3.9780 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 9 2 0 0 0 0 2 10 1 0 0 0 0 3 11 1 0 0 0 0 4 17 2 0 0 0 0 5 18 1 0 0 0 0 6 19 1 0 0 0 0 7 20 1 0 0 0 0 9 17 1 0 0 0 0 10 18 1 0 0 0 0 11 33 1 0 0 0 0 12 13 1 0 0 0 0 12 17 1 0 0 0 0 13 28 1 0 0 0 0 14 19 1 0 0 0 0 14 24 1 0 0 0 0 15 21 1 0 0 0 0 15 22 2 0 0 0 0 16 21 1 0 0 0 0 16 23 1 0 0 0 0 18 25 1 0 0 0 0 19 28 1 1 0 0 0 20 30 2 0 0 0 0 20 34 1 0 0 0 0 21 35 1 1 0 0 0 22 26 1 0 0 0 0 23 28 1 6 0 0 0 23 29 1 0 0 0 0 24 29 1 1 0 0 0 24 31 1 0 0 0 0 25 32 2 0 0 0 0 25 35 1 0 0 0 0 26 33 1 6 0 0 0 26 36 1 0 0 0 0 27 29 1 1 0 0 0 27 34 1 0 0 0 0 27 36 1 0 0 0 0 28 8 1 6 0 0 0 29 22 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	504.31
Volume:	532.82
LogP:	4.257
LogD:	3.484
LogS:	-4.456
# Rotatable Bonds:	12
TPSA:	91.29
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.252
Synthetic Accessibility Score:	5.852
Fsp3:	0.724
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:	-4.75
MDCK Permeability:	1.665882700763177e-05
Pgp-inhibitor:	0.994
Pgp-substrate:	0.078
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.021

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.109
Plasma Protein Binding (PPB):	70.7532730102539%
Volume Distribution (VD):	2.025
Pgp-substrate:	29.09797477722168%

ADMET: Metabolism

CYP1A2-inhibitor:	0.031
CYP1A2-substrate:	0.129
CYP2C19-inhibitor:	0.03
CYP2C19-substrate:	0.666
CYP2C9-inhibitor:	0.186
CYP2C9-substrate:	0.04
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.119
CYP3A4-inhibitor:	0.732
CYP3A4-substrate:	0.429

ADMET: Excretion

Clearance (CL):	4.653
Half-life (T1/2):	0.082

ADMET: Toxicity

hERG Blockers:	0.34
Human Hepatotoxicity (H-HT):	0.906
Drug-inuced Liver Injury (DILI):	0.91
AMES Toxicity:	0.811
Rat Oral Acute Toxicity:	0.882
Maximum Recommended Daily Dose:	0.972
Skin Sensitization:	0.694
Carcinogencity:	0.271
Eye Corrosion:	0.004
Eye Irritation:	0.027
Respiratory Toxicity:	0.958

Download Data

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

Natural Product: NPC471363

Natural Product ID:	NPC471363
*Common Name:**	Rel-(2S,5R,6R,8S,9S,10R,18S,19R)-19-Acetoxy-18-Ethoxy-18,19-Epoxy-2-(2-Xi-Methylbutanoyloxy)-Cleroda-3,13(16),14-Trien-6-Ol
IUPAC Name:	[(1R,3S,5S,6aR,7S,8S,10R,10aR)-1-acetyloxy-3-ethoxy-10-hydroxy-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:	TZUIFFFPPPAOBF-MJSHZTPJSA-N
Standard InCHI:	InChI=1S/C29H44O7/c1-9-17(4)12-13-28(8)19(6)14-24(31)29-22(26(33-11-3)36-27(29)34-20(7)30)15-21(16-23(28)29)35-25(32)18(5)10-2/h9,15,18-19,21,23-24,26-27,31H,1,4,10-14,16H2,2-3,5-8H3/t18?,19-,21+,23+,24+,26-,27-,28-,29-/m0/s1
SMILES:	CCO[C@H]1O[C@@H]([C@]23C1=C[C@@H](OC(=O)C(CC)C)C[C@@H]3[C@@]([C@H](C[C@H]2O)C)(C)CCC(=C)C=C)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2419870
PubChem CID:	73352259
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	=	60200.0	nM	PMID[550486]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	49800.0	nM	PMID[550486]
NPT146	Cell Line	SK-OV-3	Homo sapiens	IC50	=	15300.0	nM	PMID[550486]
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	14800.0	nM	PMID[550486]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	46900.0	nM	PMID[550486]

☑ 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 NPC471363 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	187
0.1-0.2	1022
0.2-0.3	3867
0.3-0.4	7536
0.4-0.5	13297
0.5-0.6	7621
0.6-0.7	6418
0.7-0.8	2551
0.8-0.85	89
0.85-0.9	29
0.9-0.95	44
0.95-1	36

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC238397
0.9895	High Similarity	NPC475889
0.9895	High Similarity	NPC7644
0.9895	High Similarity	NPC7613
0.9895	High Similarity	NPC134270
0.9895	High Similarity	NPC127933
0.9792	High Similarity	NPC470321
0.9792	High Similarity	NPC201880
0.9792	High Similarity	NPC473207
0.9792	High Similarity	NPC264867
0.9792	High Similarity	NPC81567
0.9691	High Similarity	NPC252296
0.9592	High Similarity	NPC88013
0.9592	High Similarity	NPC184512
0.9592	High Similarity	NPC125423
0.9574	High Similarity	NPC472188
0.9495	High Similarity	NPC48548
0.9495	High Similarity	NPC311223
0.9495	High Similarity	NPC217921
0.9495	High Similarity	NPC135015
0.9495	High Similarity	NPC128795
0.9474	High Similarity	NPC471366
0.9474	High Similarity	NPC318917
0.9474	High Similarity	NPC476800
0.9474	High Similarity	NPC472186
0.94	High Similarity	NPC40728
0.94	High Similarity	NPC316974
0.9375	High Similarity	NPC473204
0.9375	High Similarity	NPC472187
0.9375	High Similarity	NPC473545
0.9362	High Similarity	NPC471372
0.9362	High Similarity	NPC471362
0.9362	High Similarity	NPC472189
0.9307	High Similarity	NPC119550
0.9263	High Similarity	NPC171598
0.92	High Similarity	NPC109376
0.9167	High Similarity	NPC98112
0.9109	High Similarity	NPC470024
0.9109	High Similarity	NPC224660
0.91	High Similarity	NPC218158
0.91	High Similarity	NPC172867
0.9053	High Similarity	NPC88507
0.898	High Similarity	NPC20113
0.898	High Similarity	NPC477971
0.898	High Similarity	NPC161527
0.898	High Similarity	NPC219285
0.898	High Similarity	NPC477972
0.898	High Similarity	NPC228251
0.898	High Similarity	NPC477968
0.8932	High Similarity	NPC316708
0.8866	High Similarity	NPC311166
0.8846	High Similarity	NPC470026
0.8846	High Similarity	NPC17791
0.883	High Similarity	NPC470819
0.8762	High Similarity	NPC328074
0.8762	High Similarity	NPC321272
0.8762	High Similarity	NPC317460
0.8762	High Similarity	NPC470025
0.8737	High Similarity	NPC471371
0.8737	High Similarity	NPC471370
0.8737	High Similarity	NPC470817
0.8713	High Similarity	NPC120009
0.8687	High Similarity	NPC473154
0.8679	High Similarity	NPC470027
0.8673	High Similarity	NPC8954
0.8673	High Similarity	NPC94905
0.8646	High Similarity	NPC477574
0.8627	High Similarity	NPC222161
0.8571	High Similarity	NPC100892
0.8571	High Similarity	NPC477969
0.8571	High Similarity	NPC477970
0.8571	High Similarity	NPC135224
0.8557	High Similarity	NPC99653
0.8542	High Similarity	NPC469403
0.8529	High Similarity	NPC132395
0.8529	High Similarity	NPC471364
0.8529	High Similarity	NPC471365
0.8526	High Similarity	NPC263079
0.8505	High Similarity	NPC157441
0.85	High Similarity	NPC474440
0.8485	Intermediate Similarity	NPC165632
0.8476	Intermediate Similarity	NPC206618
0.8469	Intermediate Similarity	NPC189513
0.8462	Intermediate Similarity	NPC293512
0.8462	Intermediate Similarity	NPC475074
0.8454	Intermediate Similarity	NPC124374
0.8438	Intermediate Similarity	NPC261320
0.8416	Intermediate Similarity	NPC324841
0.8411	Intermediate Similarity	NPC12046
0.8411	Intermediate Similarity	NPC194951
0.84	Intermediate Similarity	NPC155319
0.84	Intermediate Similarity	NPC91197
0.84	Intermediate Similarity	NPC96597
0.84	Intermediate Similarity	NPC309503
0.84	Intermediate Similarity	NPC125551
0.84	Intermediate Similarity	NPC239547
0.8384	Intermediate Similarity	NPC286612
0.8384	Intermediate Similarity	NPC275310
0.8384	Intermediate Similarity	NPC230347
0.8384	Intermediate Similarity	NPC37603
0.8384	Intermediate Similarity	NPC471786
0.8381	Intermediate Similarity	NPC38948
0.8365	Intermediate Similarity	NPC239961
0.8365	Intermediate Similarity	NPC82251
0.8351	Intermediate Similarity	NPC220216
0.8351	Intermediate Similarity	NPC48732
0.835	Intermediate Similarity	NPC45897
0.835	Intermediate Similarity	NPC471886
0.835	Intermediate Similarity	NPC471887
0.835	Intermediate Similarity	NPC471450
0.835	Intermediate Similarity	NPC471888
0.835	Intermediate Similarity	NPC471885
0.8333	Intermediate Similarity	NPC198992
0.8333	Intermediate Similarity	NPC280991
0.8333	Intermediate Similarity	NPC474410
0.8333	Intermediate Similarity	NPC293658
0.8333	Intermediate Similarity	NPC264153
0.8317	Intermediate Similarity	NPC216478
0.8288	Intermediate Similarity	NPC122971
0.8286	Intermediate Similarity	NPC472390
0.8269	Intermediate Similarity	NPC470768
0.8252	Intermediate Similarity	NPC470571
0.8252	Intermediate Similarity	NPC37207
0.8252	Intermediate Similarity	NPC471482
0.8252	Intermediate Similarity	NPC31058
0.8252	Intermediate Similarity	NPC469606
0.8252	Intermediate Similarity	NPC273005
0.8252	Intermediate Similarity	NPC471889
0.8252	Intermediate Similarity	NPC300399
0.8247	Intermediate Similarity	NPC246028
0.8241	Intermediate Similarity	NPC473125
0.8229	Intermediate Similarity	NPC471779
0.8224	Intermediate Similarity	NPC83005
0.8211	Intermediate Similarity	NPC119001
0.8208	Intermediate Similarity	NPC325054
0.82	Intermediate Similarity	NPC13924
0.82	Intermediate Similarity	NPC276110
0.8198	Intermediate Similarity	NPC473617
0.8198	Intermediate Similarity	NPC473828
0.819	Intermediate Similarity	NPC470763
0.819	Intermediate Similarity	NPC469607
0.819	Intermediate Similarity	NPC127609
0.819	Intermediate Similarity	NPC470767
0.8182	Intermediate Similarity	NPC472812
0.8173	Intermediate Similarity	NPC23584
0.8165	Intermediate Similarity	NPC290608
0.8165	Intermediate Similarity	NPC40133
0.8165	Intermediate Similarity	NPC311592
0.8165	Intermediate Similarity	NPC473128
0.8165	Intermediate Similarity	NPC49413
0.8165	Intermediate Similarity	NPC44298
0.8165	Intermediate Similarity	NPC75167
0.8158	Intermediate Similarity	NPC41129
0.8155	Intermediate Similarity	NPC475617
0.8144	Intermediate Similarity	NPC69713
0.8137	Intermediate Similarity	NPC477928
0.8131	Intermediate Similarity	NPC112457
0.8131	Intermediate Similarity	NPC31522
0.8125	Intermediate Similarity	NPC470914
0.8125	Intermediate Similarity	NPC477071
0.8119	Intermediate Similarity	NPC284194
0.8119	Intermediate Similarity	NPC471765
0.8119	Intermediate Similarity	NPC221801
0.8119	Intermediate Similarity	NPC211810
0.8108	Intermediate Similarity	NPC23046
0.8105	Intermediate Similarity	NPC471367
0.81	Intermediate Similarity	NPC298973
0.81	Intermediate Similarity	NPC57117
0.81	Intermediate Similarity	NPC178949
0.81	Intermediate Similarity	NPC211238
0.81	Intermediate Similarity	NPC472416
0.81	Intermediate Similarity	NPC470255
0.81	Intermediate Similarity	NPC96736
0.81	Intermediate Similarity	NPC104925
0.81	Intermediate Similarity	NPC472360
0.81	Intermediate Similarity	NPC105490
0.81	Intermediate Similarity	NPC250075
0.8095	Intermediate Similarity	NPC85593
0.8095	Intermediate Similarity	NPC31430
0.8091	Intermediate Similarity	NPC181145
0.8091	Intermediate Similarity	NPC475163
0.8081	Intermediate Similarity	NPC234335
0.8081	Intermediate Similarity	NPC472811
0.8081	Intermediate Similarity	NPC72845
0.8077	Intermediate Similarity	NPC472552
0.8077	Intermediate Similarity	NPC472815
0.8077	Intermediate Similarity	NPC11956
0.8077	Intermediate Similarity	NPC475344
0.8077	Intermediate Similarity	NPC121423
0.8077	Intermediate Similarity	NPC476471
0.8077	Intermediate Similarity	NPC154452
0.8077	Intermediate Similarity	NPC476081
0.8061	Intermediate Similarity	NPC470734
0.8061	Intermediate Similarity	NPC16265
0.8061	Intermediate Similarity	NPC293044
0.8058	Intermediate Similarity	NPC47024
0.8058	Intermediate Similarity	NPC477721
0.8058	Intermediate Similarity	NPC146188
0.8058	Intermediate Similarity	NPC477716
0.8056	Intermediate Similarity	NPC177047

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 NPC471363 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	153
0.1-0.2	1273
0.2-0.3	3629
0.3-0.4	2569
0.4-0.5	971
0.5-0.6	302
0.6-0.7	228
0.7-0.8	25
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
0.7961	Intermediate Similarity	NPD7638	Approved
0.7885	Intermediate Similarity	NPD7640	Approved
0.7885	Intermediate Similarity	NPD7639	Approved
0.787	Intermediate Similarity	NPD6686	Approved
0.7672	Intermediate Similarity	NPD7503	Approved
0.7619	Intermediate Similarity	NPD4225	Approved
0.7565	Intermediate Similarity	NPD7328	Approved
0.7565	Intermediate Similarity	NPD7327	Approved
0.7521	Intermediate Similarity	NPD8515	Approved
0.7521	Intermediate Similarity	NPD8516	Approved
0.7521	Intermediate Similarity	NPD8033	Approved
0.7521	Intermediate Similarity	NPD8513	Phase 3
0.7521	Intermediate Similarity	NPD8517	Approved
0.75	Intermediate Similarity	NPD7516	Approved
0.7436	Intermediate Similarity	NPD8377	Approved
0.7436	Intermediate Similarity	NPD8294	Approved
0.7417	Intermediate Similarity	NPD7507	Approved
0.7379	Intermediate Similarity	NPD7637	Suspended
0.7374	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.7373	Intermediate Similarity	NPD8378	Approved
0.7373	Intermediate Similarity	NPD8380	Approved
0.7373	Intermediate Similarity	NPD8335	Approved
0.7373	Intermediate Similarity	NPD8379	Approved
0.7373	Intermediate Similarity	NPD8296	Approved
0.7321	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD5778	Approved
0.7308	Intermediate Similarity	NPD5779	Approved
0.7297	Intermediate Similarity	NPD6412	Phase 2
0.7248	Intermediate Similarity	NPD7632	Discontinued
0.7236	Intermediate Similarity	NPD7319	Approved
0.7217	Intermediate Similarity	NPD8133	Approved
0.7168	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD6370	Approved
0.7156	Intermediate Similarity	NPD5344	Discontinued
0.7154	Intermediate Similarity	NPD7736	Approved
0.7143	Intermediate Similarity	NPD6399	Phase 3
0.713	Intermediate Similarity	NPD6882	Approved
0.713	Intermediate Similarity	NPD8029	Clinical (unspecified phase)
0.7073	Intermediate Similarity	NPD8293	Discontinued
0.7064	Intermediate Similarity	NPD6648	Approved
0.7049	Intermediate Similarity	NPD7492	Approved
0.7048	Intermediate Similarity	NPD6411	Approved
0.7034	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD7115	Discovery
0.7	Intermediate Similarity	NPD6054	Approved
0.6992	Remote Similarity	NPD6616	Approved
0.6967	Remote Similarity	NPD8328	Phase 3
0.6961	Remote Similarity	NPD1694	Approved
0.6957	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6952	Remote Similarity	NPD7838	Discovery
0.6935	Remote Similarity	NPD8074	Phase 3
0.6935	Remote Similarity	NPD7078	Approved
0.693	Remote Similarity	NPD6881	Approved
0.693	Remote Similarity	NPD6899	Approved
0.6916	Remote Similarity	NPD7748	Approved
0.6903	Remote Similarity	NPD7128	Approved
0.6903	Remote Similarity	NPD5739	Approved
0.6903	Remote Similarity	NPD6675	Approved
0.6903	Remote Similarity	NPD6402	Approved
0.6897	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6891	Remote Similarity	NPD6009	Approved
0.6887	Remote Similarity	NPD7515	Phase 2
0.6881	Remote Similarity	NPD7902	Approved
0.6863	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.686	Remote Similarity	NPD6059	Approved
0.6857	Remote Similarity	NPD6101	Approved
0.6857	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD5697	Approved
0.6838	Remote Similarity	NPD6053	Discontinued
0.6829	Remote Similarity	NPD6067	Discontinued
0.6827	Remote Similarity	NPD4251	Approved
0.6827	Remote Similarity	NPD4250	Approved
0.681	Remote Similarity	NPD6883	Approved
0.681	Remote Similarity	NPD7290	Approved
0.681	Remote Similarity	NPD7102	Approved
0.6803	Remote Similarity	NPD6016	Approved
0.6803	Remote Similarity	NPD6015	Approved
0.6792	Remote Similarity	NPD6698	Approved
0.6792	Remote Similarity	NPD46	Approved
0.6783	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6783	Remote Similarity	NPD7320	Approved
0.6765	Remote Similarity	NPD6695	Phase 3
0.6754	Remote Similarity	NPD6008	Approved
0.6752	Remote Similarity	NPD6617	Approved
0.6752	Remote Similarity	NPD6869	Approved
0.6752	Remote Similarity	NPD6649	Approved
0.6752	Remote Similarity	NPD6847	Approved
0.6752	Remote Similarity	NPD6650	Approved
0.6752	Remote Similarity	NPD8130	Phase 1
0.6748	Remote Similarity	NPD5988	Approved
0.6731	Remote Similarity	NPD4249	Approved
0.6724	Remote Similarity	NPD6014	Approved
0.6724	Remote Similarity	NPD6373	Approved
0.6724	Remote Similarity	NPD6372	Approved
0.6724	Remote Similarity	NPD6013	Approved
0.6724	Remote Similarity	NPD6012	Approved
0.67	Remote Similarity	NPD7645	Phase 2
0.6699	Remote Similarity	NPD4786	Approved
0.6698	Remote Similarity	NPD6051	Approved
0.6696	Remote Similarity	NPD5701	Approved
0.6696	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6695	Remote Similarity	NPD8297	Approved
0.6667	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD3667	Approved
0.6639	Remote Similarity	NPD4632	Approved
0.6638	Remote Similarity	NPD6011	Approved
0.6634	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6634	Remote Similarity	NPD7525	Registered
0.6633	Remote Similarity	NPD8264	Approved
0.6606	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6606	Remote Similarity	NPD7900	Approved
0.6585	Remote Similarity	NPD6319	Approved
0.6577	Remote Similarity	NPD6084	Phase 2
0.6577	Remote Similarity	NPD6083	Phase 2
0.6574	Remote Similarity	NPD6079	Approved
0.6574	Remote Similarity	NPD7983	Approved
0.6574	Remote Similarity	NPD8035	Phase 2
0.6574	Remote Similarity	NPD8034	Phase 2
0.6571	Remote Similarity	NPD3618	Phase 1
0.6545	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6542	Remote Similarity	NPD5328	Approved
0.6535	Remote Similarity	NPD6929	Approved
0.6509	Remote Similarity	NPD7524	Approved
0.6509	Remote Similarity	NPD7750	Discontinued
0.6491	Remote Similarity	NPD5211	Phase 2
0.6486	Remote Similarity	NPD7839	Suspended
0.6476	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6476	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD6931	Approved
0.6471	Remote Similarity	NPD4819	Approved
0.6471	Remote Similarity	NPD4820	Approved
0.6471	Remote Similarity	NPD6930	Phase 2
0.6471	Remote Similarity	NPD4822	Approved
0.6471	Remote Similarity	NPD7332	Phase 2
0.6471	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD7514	Phase 3
0.6471	Remote Similarity	NPD4821	Approved
0.6465	Remote Similarity	NPD8039	Approved
0.6465	Remote Similarity	NPD6942	Approved
0.6465	Remote Similarity	NPD7339	Approved
0.646	Remote Similarity	NPD5285	Approved
0.646	Remote Similarity	NPD4696	Approved
0.646	Remote Similarity	NPD5286	Approved
0.6442	Remote Similarity	NPD7154	Phase 3
0.6436	Remote Similarity	NPD7145	Approved
0.6436	Remote Similarity	NPD4268	Approved
0.6436	Remote Similarity	NPD4271	Approved
0.6429	Remote Similarity	NPD7604	Phase 2
0.6429	Remote Similarity	NPD4755	Approved
0.6415	Remote Similarity	NPD7521	Approved
0.6415	Remote Similarity	NPD7146	Approved
0.6415	Remote Similarity	NPD5330	Approved
0.6415	Remote Similarity	NPD6684	Approved
0.6415	Remote Similarity	NPD7334	Approved
0.6415	Remote Similarity	NPD6409	Approved
0.6408	Remote Similarity	NPD6902	Approved
0.64	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.64	Remote Similarity	NPD5983	Phase 2
0.6396	Remote Similarity	NPD5695	Phase 3
0.6387	Remote Similarity	NPD6371	Approved
0.6379	Remote Similarity	NPD5141	Approved
0.6371	Remote Similarity	NPD7100	Approved
0.6371	Remote Similarity	NPD7101	Approved
0.6364	Remote Similarity	NPD4202	Approved
0.6357	Remote Similarity	NPD6033	Approved
0.6355	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.6348	Remote Similarity	NPD5225	Approved
0.6348	Remote Similarity	NPD4633	Approved
0.6348	Remote Similarity	NPD5224	Approved
0.6348	Remote Similarity	NPD5226	Approved
0.6339	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6339	Remote Similarity	NPD5222	Approved
0.6339	Remote Similarity	NPD5221	Approved
0.6337	Remote Similarity	NPD6932	Approved
0.6337	Remote Similarity	NPD6925	Approved
0.6337	Remote Similarity	NPD5776	Phase 2
0.6336	Remote Similarity	NPD7260	Phase 2
0.633	Remote Similarity	NPD5785	Approved
0.6328	Remote Similarity	NPD6336	Discontinued
0.6316	Remote Similarity	NPD4700	Approved
0.6306	Remote Similarity	NPD5282	Discontinued
0.6296	Remote Similarity	NPD6672	Approved
0.6296	Remote Similarity	NPD6903	Approved
0.6296	Remote Similarity	NPD5737	Approved
0.6296	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6293	Remote Similarity	NPD5174	Approved
0.6293	Remote Similarity	NPD5175	Approved
0.629	Remote Similarity	NPD6335	Approved
0.6286	Remote Similarity	NPD5362	Discontinued
0.6283	Remote Similarity	NPD5173	Approved
0.6275	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6273	Remote Similarity	NPD5281	Approved
0.6273	Remote Similarity	NPD5284	Approved
0.6273	Remote Similarity	NPD7087	Discontinued
0.6271	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6261	Remote Similarity	NPD5223	Approved
0.626	Remote Similarity	NPD6274	Approved
0.626	Remote Similarity	NPD6868	Approved
0.625	Remote Similarity	NPD4634	Approved
0.625	Remote Similarity	NPD6356	Clinical (unspecified phase)

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