NPASS Compound

Structure

CID17791 OpenBabel06191715342D 46 48 0 0 1 0 0 0 0 0999 V2000 -9.6614 2.8578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7930 0.6361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8134 -1.0606 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7229 0.4088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3672 2.3680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7094 0.5611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9825 2.2852 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3644 -1.9089 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8131 3.3476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8134 0.6361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9647 2.8578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1164 3.3476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2680 2.8578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4197 3.3476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5713 2.8578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7229 3.3476 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8746 2.8578 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3440 -0.2122 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8542 -1.0606 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3295 -2.5300 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 -2.5300 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3236 -0.2122 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8746 -0.0810 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5188 1.8782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0121 -0.3706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3270 1.5572 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1779 -3.0198 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3295 -1.5504 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 -1.5504 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8746 1.8782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 0.4088 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1779 -0.0810 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3984 -0.8949 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9742 -0.1024 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8746 -1.0606 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1779 -1.0606 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3295 2.3680 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9703 -0.5743 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3688 1.7609 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1779 -3.9994 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7229 1.3884 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5188 0.8986 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3566 -1.0986 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6297 0.6256 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 1.3884 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 1 0 0 0 0 2 10 2 0 0 0 0 3 22 2 0 0 0 0 4 23 1 0 0 0 0 5 24 1 0 0 0 0 6 25 1 0 0 0 0 7 26 1 0 0 0 0 9 11 1 0 0 0 0 10 22 1 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 17 30 1 0 0 0 0 18 19 1 0 0 0 0 18 22 1 0 0 0 0 19 35 1 0 0 0 0 20 27 1 0 0 0 0 20 28 2 0 0 0 0 21 27 1 0 0 0 0 21 29 1 0 0 0 0 23 31 1 0 0 0 0 23 35 1 6 0 0 0 24 37 2 0 0 0 0 24 42 1 0 0 0 0 25 38 2 0 0 0 0 25 43 1 0 0 0 0 26 39 2 0 0 0 0 26 44 1 0 0 0 0 27 40 1 6 0 0 0 28 33 1 0 0 0 0 29 35 1 1 0 0 0 29 36 1 0 0 0 0 30 41 2 0 0 0 0 30 45 1 0 0 0 0 31 32 1 0 0 0 0 31 45 1 1 0 0 0 32 36 1 6 0 0 0 32 42 1 0 0 0 0 33 43 1 6 0 0 0 33 46 1 0 0 0 0 34 36 1 1 0 0 0 34 44 1 0 0 0 0 34 46 1 0 0 0 0 35 8 1 1 0 0 0 36 28 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	642.34
Volume:	669.717
LogP:	5.039
LogD:	2.488
LogS:	-4.942
# Rotatable Bonds:	18
TPSA:	134.66
# H-Bond Aceptor:	10
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.062
Synthetic Accessibility Score:	6.009
Fsp3:	0.611
Lipinski Rule-of-5:	Rejected
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:	-4.891
MDCK Permeability:	7.426249067066237e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.827
Human Intestinal Absorption (HIA):	0.019
20% Bioavailability (F20%):	0.977
30% Bioavailability (F30%):	0.771

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.332
Plasma Protein Binding (PPB):	83.11080169677734%
Volume Distribution (VD):	2.158
Pgp-substrate:	8.504833221435547%

ADMET: Metabolism

CYP1A2-inhibitor:	0.086
CYP1A2-substrate:	0.047
CYP2C19-inhibitor:	0.148
CYP2C19-substrate:	0.099
CYP2C9-inhibitor:	0.613
CYP2C9-substrate:	0.073
CYP2D6-inhibitor:	0.048
CYP2D6-substrate:	0.05
CYP3A4-inhibitor:	0.823
CYP3A4-substrate:	0.329

ADMET: Excretion

Clearance (CL):	2.837
Half-life (T1/2):	0.175

ADMET: Toxicity

hERG Blockers:	0.505
Human Hepatotoxicity (H-HT):	0.966
Drug-inuced Liver Injury (DILI):	0.944
AMES Toxicity:	0.759
Rat Oral Acute Toxicity:	0.928
Maximum Recommended Daily Dose:	0.971
Skin Sensitization:	0.953
Carcinogencity:	0.186
Eye Corrosion:	0.006
Eye Irritation:	0.012
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: NPC17791

Natural Product ID:	NPC17791
*Common Name:**	Casearupestrin D
IUPAC Name:	[(1R,3R,5R,6aS,7S,8S,9R,10R,10aS)-1,3,10-triacetyloxy-5-hydroxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-9-yl] (2Z,4E)-deca-2,4-dienoate
Synonyms:	casearupestrin D
Standard InCHIKey:	KAIWHFAEAXEXOF-PDNIMGFCSA-N
Standard InCHI:	InChI=1S/C36H50O10/c1-9-11-12-13-14-15-16-17-30(41)45-31-23(4)35(8,19-18-22(3)10-2)29-21-27(40)20-28-33(43-25(6)38)46-34(44-26(7)39)36(28,29)32(31)42-24(5)37/h10,14-17,20,23,27,29,31-34,40H,2-3,9,11-13,18-19,21H2,1,4-8H3/b15-14+,17-16-/t23-,27+,29+,31-,32+,33+,34+,35-,36-/m1/s1
SMILES:	CCCCC/C=C/C=CC(=O)O[C@@H]1[C@@H](C)[C@@](C)(CCC(=C)C=C)[C@H]2[C@]3([C@H]1OC(=O)C)[C@@H](OC(=O)C)O[C@@H](C3=C[C@@H](C2)O)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1774420
PubChem CID:	52951399
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
NPO2718	Casearia rupestris	Species	Salicaceae	Eukaryota	leaves	n.a.	n.a.	PMID[21381705]
NPO2718	Casearia rupestris	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21381705]
NPO2718	Casearia rupestris	Species	Salicaceae	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	4

Activity Type	# Activity
Cell Line	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	250.0	nM	PMID[523180]
NPT400	Cell Line	MDA-MB-435	Homo sapiens	IC50	=	930.0	nM	PMID[523180]
NPT180	Cell Line	HCT-8	Homo sapiens	IC50	=	250.0	nM	PMID[523180]
NPT399	Cell Line	SF-295	Homo sapiens	IC50	=	430.0	nM	PMID[523180]

☑ 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 NPC17791 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	198
0.1-0.2	1188
0.2-0.3	3819
0.3-0.4	6525
0.4-0.5	13749
0.5-0.6	8928
0.6-0.7	5822
0.7-0.8	2291
0.8-0.85	86
0.85-0.9	51
0.9-0.95	26
0.95-1	14

Similarity Score	Similarity Level	Natural Product ID
0.9903	High Similarity	NPC317460
0.9903	High Similarity	NPC321272
0.9903	High Similarity	NPC470025
0.9903	High Similarity	NPC328074
0.9808	High Similarity	NPC470027
0.9709	High Similarity	NPC316708
0.9706	High Similarity	NPC470024
0.9615	High Similarity	NPC470026
0.9608	High Similarity	NPC109376
0.9515	High Similarity	NPC224660
0.951	High Similarity	NPC172867
0.9238	High Similarity	NPC40728
0.9238	High Similarity	NPC316974
0.9143	High Similarity	NPC217921
0.9143	High Similarity	NPC311223
0.9143	High Similarity	NPC128795
0.9143	High Similarity	NPC135015
0.9143	High Similarity	NPC48548
0.9135	High Similarity	NPC218158
0.9048	High Similarity	NPC88013
0.9048	High Similarity	NPC125423
0.9038	High Similarity	NPC470321
0.9038	High Similarity	NPC201880
0.9038	High Similarity	NPC264867
0.9038	High Similarity	NPC473207
0.9038	High Similarity	NPC81567
0.8972	High Similarity	NPC119550
0.8942	High Similarity	NPC7613
0.8942	High Similarity	NPC134270
0.8942	High Similarity	NPC127933
0.8942	High Similarity	NPC7644
0.8942	High Similarity	NPC475889
0.8868	High Similarity	NPC184512
0.8846	High Similarity	NPC238397
0.8846	High Similarity	NPC471363
0.8824	High Similarity	NPC98112
0.8774	High Similarity	NPC252296
0.8725	High Similarity	NPC171598
0.8704	High Similarity	NPC206618
0.8673	High Similarity	NPC470914
0.8654	High Similarity	NPC472187
0.8654	High Similarity	NPC473545
0.8654	High Similarity	NPC473204
0.8627	High Similarity	NPC472189
0.8627	High Similarity	NPC471362
0.8627	High Similarity	NPC471372
0.8624	High Similarity	NPC177047
0.8611	High Similarity	NPC38948
0.8598	High Similarity	NPC82251
0.8559	High Similarity	NPC473159
0.8559	High Similarity	NPC264153
0.8558	High Similarity	NPC471366
0.8558	High Similarity	NPC472186
0.8558	High Similarity	NPC318917
0.8558	High Similarity	NPC476800
0.8519	High Similarity	NPC472390
0.8505	High Similarity	NPC470768
0.8491	Intermediate Similarity	NPC11956
0.8462	Intermediate Similarity	NPC472188
0.8448	Intermediate Similarity	NPC471082
0.8426	Intermediate Similarity	NPC239961
0.8426	Intermediate Similarity	NPC470763
0.8426	Intermediate Similarity	NPC470767
0.8421	Intermediate Similarity	NPC473828
0.8421	Intermediate Similarity	NPC473617
0.8411	Intermediate Similarity	NPC23584
0.8411	Intermediate Similarity	NPC281378
0.8411	Intermediate Similarity	NPC120009
0.8396	Intermediate Similarity	NPC472554
0.8396	Intermediate Similarity	NPC198992
0.8381	Intermediate Similarity	NPC474440
0.8364	Intermediate Similarity	NPC475586
0.8362	Intermediate Similarity	NPC233500
0.8349	Intermediate Similarity	NPC471205
0.8349	Intermediate Similarity	NPC475074
0.8348	Intermediate Similarity	NPC219656
0.8333	Intermediate Similarity	NPC23046
0.8333	Intermediate Similarity	NPC473543
0.8333	Intermediate Similarity	NPC473968
0.8318	Intermediate Similarity	NPC476471
0.8318	Intermediate Similarity	NPC201191
0.8318	Intermediate Similarity	NPC475344
0.8318	Intermediate Similarity	NPC150463
0.8318	Intermediate Similarity	NPC470571
0.8318	Intermediate Similarity	NPC472815
0.8318	Intermediate Similarity	NPC472552
0.8304	Intermediate Similarity	NPC473125
0.8302	Intermediate Similarity	NPC161527
0.8302	Intermediate Similarity	NPC219285
0.8302	Intermediate Similarity	NPC324841
0.8302	Intermediate Similarity	NPC20113
0.8302	Intermediate Similarity	NPC477968
0.8302	Intermediate Similarity	NPC477972
0.8302	Intermediate Similarity	NPC477971
0.8302	Intermediate Similarity	NPC228251
0.8291	Intermediate Similarity	NPC196130
0.8276	Intermediate Similarity	NPC48692
0.8273	Intermediate Similarity	NPC50124
0.8273	Intermediate Similarity	NPC475263
0.8261	Intermediate Similarity	NPC470515
0.8257	Intermediate Similarity	NPC51719
0.8246	Intermediate Similarity	NPC207637
0.8241	Intermediate Similarity	NPC474124
0.8241	Intermediate Similarity	NPC473523
0.8241	Intermediate Similarity	NPC474575
0.8241	Intermediate Similarity	NPC45897
0.8235	Intermediate Similarity	NPC470817
0.8235	Intermediate Similarity	NPC469403
0.823	Intermediate Similarity	NPC49413
0.823	Intermediate Similarity	NPC290608
0.823	Intermediate Similarity	NPC473128
0.823	Intermediate Similarity	NPC40133
0.823	Intermediate Similarity	NPC44298
0.8224	Intermediate Similarity	NPC280991
0.822	Intermediate Similarity	NPC219804
0.8208	Intermediate Similarity	NPC473154
0.8205	Intermediate Similarity	NPC476204
0.8205	Intermediate Similarity	NPC170084
0.819	Intermediate Similarity	NPC470517
0.819	Intermediate Similarity	NPC221801
0.819	Intermediate Similarity	NPC471765
0.819	Intermediate Similarity	NPC470915
0.819	Intermediate Similarity	NPC122971
0.819	Intermediate Similarity	NPC284194
0.819	Intermediate Similarity	NPC165632
0.819	Intermediate Similarity	NPC470911
0.819	Intermediate Similarity	NPC211810
0.8182	Intermediate Similarity	NPC473586
0.8182	Intermediate Similarity	NPC122816
0.8174	Intermediate Similarity	NPC203862
0.8173	Intermediate Similarity	NPC472416
0.8173	Intermediate Similarity	NPC470255
0.8173	Intermediate Similarity	NPC469491
0.8173	Intermediate Similarity	NPC88507
0.8173	Intermediate Similarity	NPC472360
0.8158	Intermediate Similarity	NPC475163
0.8151	Intermediate Similarity	NPC86346
0.8151	Intermediate Similarity	NPC75856
0.8151	Intermediate Similarity	NPC469379
0.8148	Intermediate Similarity	NPC214277
0.8148	Intermediate Similarity	NPC121423
0.8142	Intermediate Similarity	NPC231797
0.8137	Intermediate Similarity	NPC246028
0.8137	Intermediate Similarity	NPC470819
0.8131	Intermediate Similarity	NPC64348
0.8131	Intermediate Similarity	NPC38855
0.8125	Intermediate Similarity	NPC235014
0.812	Intermediate Similarity	NPC135369
0.8113	Intermediate Similarity	NPC91197
0.8113	Intermediate Similarity	NPC309503
0.8113	Intermediate Similarity	NPC155319
0.8113	Intermediate Similarity	NPC96597
0.8113	Intermediate Similarity	NPC125551
0.8113	Intermediate Similarity	NPC239547
0.8113	Intermediate Similarity	NPC120446
0.8113	Intermediate Similarity	NPC473244
0.8108	Intermediate Similarity	NPC181994
0.8103	Intermediate Similarity	NPC234522
0.8095	Intermediate Similarity	NPC286612
0.8095	Intermediate Similarity	NPC230347
0.8095	Intermediate Similarity	NPC275310
0.8091	Intermediate Similarity	NPC470055
0.8091	Intermediate Similarity	NPC88349
0.8091	Intermediate Similarity	NPC470056
0.8091	Intermediate Similarity	NPC471206
0.8087	Intermediate Similarity	NPC471816
0.8083	Intermediate Similarity	NPC179261
0.8077	Intermediate Similarity	NPC472812
0.8073	Intermediate Similarity	NPC473070
0.807	Intermediate Similarity	NPC469454
0.807	Intermediate Similarity	NPC157441
0.807	Intermediate Similarity	NPC287075
0.807	Intermediate Similarity	NPC474410
0.807	Intermediate Similarity	NPC293658
0.807	Intermediate Similarity	NPC469463
0.807	Intermediate Similarity	NPC469496
0.8067	Intermediate Similarity	NPC41129
0.8067	Intermediate Similarity	NPC469382
0.8056	Intermediate Similarity	NPC477717
0.8056	Intermediate Similarity	NPC475617
0.8053	Intermediate Similarity	NPC208189
0.8053	Intermediate Similarity	NPC65034
0.8051	Intermediate Similarity	NPC202051
0.8049	Intermediate Similarity	NPC230331
0.8037	Intermediate Similarity	NPC477928
0.8036	Intermediate Similarity	NPC257853
0.8034	Intermediate Similarity	NPC44899
0.8034	Intermediate Similarity	NPC304260
0.8034	Intermediate Similarity	NPC476529
0.8034	Intermediate Similarity	NPC153085
0.8034	Intermediate Similarity	NPC475775
0.8034	Intermediate Similarity	NPC268326
0.8034	Intermediate Similarity	NPC29639
0.8034	Intermediate Similarity	NPC5883
0.8033	Intermediate Similarity	NPC476966
0.8033	Intermediate Similarity	NPC471407
0.8019	Intermediate Similarity	NPC8954
0.8019	Intermediate Similarity	NPC473153
0.8019	Intermediate Similarity	NPC94905
0.8019	Intermediate Similarity	NPC311166

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 NPC17791 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	170
0.1-0.2	1345
0.2-0.3	3618
0.3-0.4	2592
0.4-0.5	921
0.5-0.6	313
0.6-0.7	167
0.7-0.8	24
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
0.8205	Intermediate Similarity	NPD7503	Approved
0.7946	Intermediate Similarity	NPD6686	Approved
0.7899	Intermediate Similarity	NPD8033	Approved
0.7881	Intermediate Similarity	NPD7516	Approved
0.7815	Intermediate Similarity	NPD8377	Approved
0.7815	Intermediate Similarity	NPD8294	Approved
0.7798	Intermediate Similarity	NPD6648	Approved
0.7797	Intermediate Similarity	NPD7327	Approved
0.7797	Intermediate Similarity	NPD7328	Approved
0.775	Intermediate Similarity	NPD8296	Approved
0.775	Intermediate Similarity	NPD8380	Approved
0.775	Intermediate Similarity	NPD8378	Approved
0.775	Intermediate Similarity	NPD8335	Approved
0.775	Intermediate Similarity	NPD8379	Approved
0.7727	Intermediate Similarity	NPD5344	Discontinued
0.7706	Intermediate Similarity	NPD8029	Clinical (unspecified phase)
0.7706	Intermediate Similarity	NPD4225	Approved
0.7603	Intermediate Similarity	NPD8516	Approved
0.7603	Intermediate Similarity	NPD8517	Approved
0.7603	Intermediate Similarity	NPD8513	Phase 3
0.7603	Intermediate Similarity	NPD8515	Approved
0.7547	Intermediate Similarity	NPD7838	Discovery
0.7477	Intermediate Similarity	NPD7639	Approved
0.7477	Intermediate Similarity	NPD7640	Approved
0.7387	Intermediate Similarity	NPD7638	Approved
0.736	Intermediate Similarity	NPD7507	Approved
0.7308	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.7265	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7244	Intermediate Similarity	NPD7736	Approved
0.7188	Intermediate Similarity	NPD7319	Approved
0.7131	Intermediate Similarity	NPD7115	Discovery
0.712	Intermediate Similarity	NPD6370	Approved
0.7119	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7094	Intermediate Similarity	NPD6412	Phase 2
0.7063	Intermediate Similarity	NPD8328	Phase 3
0.7059	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7031	Intermediate Similarity	NPD8293	Discontinued
0.7031	Intermediate Similarity	NPD8074	Phase 3
0.7025	Intermediate Similarity	NPD8133	Approved
0.7008	Intermediate Similarity	NPD7492	Approved
0.696	Remote Similarity	NPD6054	Approved
0.6953	Remote Similarity	NPD6616	Approved
0.6942	Remote Similarity	NPD8297	Approved
0.6942	Remote Similarity	NPD6882	Approved
0.6899	Remote Similarity	NPD7078	Approved
0.6897	Remote Similarity	NPD7632	Discontinued
0.686	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD6009	Approved
0.6847	Remote Similarity	NPD7637	Suspended
0.6807	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6789	Remote Similarity	NPD7524	Approved
0.6786	Remote Similarity	NPD5779	Approved
0.6786	Remote Similarity	NPD5778	Approved
0.6772	Remote Similarity	NPD6016	Approved
0.6772	Remote Similarity	NPD6015	Approved
0.6757	Remote Similarity	NPD46	Approved
0.6757	Remote Similarity	NPD6698	Approved
0.6719	Remote Similarity	NPD5988	Approved
0.6696	Remote Similarity	NPD7983	Approved
0.6693	Remote Similarity	NPD6319	Approved
0.6693	Remote Similarity	NPD6059	Approved
0.6667	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6067	Discontinued
0.6613	Remote Similarity	NPD4632	Approved
0.6612	Remote Similarity	NPD6881	Approved
0.6612	Remote Similarity	NPD6899	Approved
0.6606	Remote Similarity	NPD1694	Approved
0.6602	Remote Similarity	NPD8264	Approved
0.6585	Remote Similarity	NPD6650	Approved
0.6585	Remote Similarity	NPD6649	Approved
0.6585	Remote Similarity	NPD8130	Phase 1
0.6579	Remote Similarity	NPD7748	Approved
0.6574	Remote Similarity	NPD6695	Phase 3
0.6567	Remote Similarity	NPD7260	Phase 2
0.6552	Remote Similarity	NPD7902	Approved
0.6538	Remote Similarity	NPD7829	Approved
0.6538	Remote Similarity	NPD7830	Approved
0.6529	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6529	Remote Similarity	NPD5697	Approved
0.6504	Remote Similarity	NPD6883	Approved
0.6504	Remote Similarity	NPD7290	Approved
0.6504	Remote Similarity	NPD7102	Approved
0.6504	Remote Similarity	NPD6371	Approved
0.6486	Remote Similarity	NPD7750	Discontinued
0.6475	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6452	Remote Similarity	NPD6847	Approved
0.6452	Remote Similarity	NPD6869	Approved
0.6452	Remote Similarity	NPD6617	Approved
0.6446	Remote Similarity	NPD6675	Approved
0.6446	Remote Similarity	NPD6402	Approved
0.6446	Remote Similarity	NPD7128	Approved
0.6446	Remote Similarity	NPD5739	Approved
0.6423	Remote Similarity	NPD6012	Approved
0.6423	Remote Similarity	NPD6014	Approved
0.6423	Remote Similarity	NPD6372	Approved
0.6423	Remote Similarity	NPD6013	Approved
0.6423	Remote Similarity	NPD6373	Approved
0.6412	Remote Similarity	NPD7604	Phase 2
0.6404	Remote Similarity	NPD7515	Phase 2
0.6404	Remote Similarity	NPD6411	Approved
0.64	Remote Similarity	NPD6053	Discontinued
0.6389	Remote Similarity	NPD7625	Phase 1
0.6385	Remote Similarity	NPD5983	Phase 2
0.6355	Remote Similarity	NPD6929	Approved
0.6348	Remote Similarity	NPD6399	Phase 3
0.6341	Remote Similarity	NPD6011	Approved
0.6341	Remote Similarity	NPD7320	Approved
0.6333	Remote Similarity	NPD5211	Phase 2
0.6331	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.633	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6325	Remote Similarity	NPD7839	Suspended
0.6316	Remote Similarity	NPD6336	Discontinued
0.6311	Remote Similarity	NPD6008	Approved
0.6296	Remote Similarity	NPD6931	Approved
0.6296	Remote Similarity	NPD7514	Phase 3
0.6296	Remote Similarity	NPD6930	Phase 2
0.6296	Remote Similarity	NPD7332	Phase 2
0.6293	Remote Similarity	NPD7900	Approved
0.6293	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6289	Remote Similarity	NPD7799	Discontinued
0.6277	Remote Similarity	NPD6845	Suspended
0.6262	Remote Similarity	NPD7145	Approved
0.6261	Remote Similarity	NPD6079	Approved
0.626	Remote Similarity	NPD5701	Approved
0.6239	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6239	Remote Similarity	NPD6902	Approved
0.623	Remote Similarity	NPD5141	Approved
0.6228	Remote Similarity	NPD6051	Approved
0.6228	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6228	Remote Similarity	NPD6101	Approved
0.6222	Remote Similarity	NPD6033	Approved
0.6204	Remote Similarity	NPD7645	Phase 2
0.6195	Remote Similarity	NPD4251	Approved
0.6195	Remote Similarity	NPD4250	Approved
0.6194	Remote Similarity	NPD8451	Approved
0.6181	Remote Similarity	NPD7266	Discontinued
0.6174	Remote Similarity	NPD3168	Discontinued
0.6174	Remote Similarity	NPD5785	Approved
0.6168	Remote Similarity	NPD5776	Phase 2
0.6168	Remote Similarity	NPD6925	Approved
0.6167	Remote Similarity	NPD5286	Approved
0.6167	Remote Similarity	NPD4696	Approved
0.6167	Remote Similarity	NPD5285	Approved
0.6154	Remote Similarity	NPD7641	Discontinued
0.6149	Remote Similarity	NPD8470	Clinical (unspecified phase)
0.6148	Remote Similarity	NPD8448	Approved
0.6147	Remote Similarity	NPD7525	Registered
0.6136	Remote Similarity	NPD8444	Approved
0.6134	Remote Similarity	NPD6084	Phase 2
0.6134	Remote Similarity	NPD6083	Phase 2
0.6122	Remote Similarity	NPD7274	Clinical (unspecified phase)
0.6121	Remote Similarity	NPD7087	Discontinued
0.6119	Remote Similarity	NPD8342	Approved
0.6119	Remote Similarity	NPD8340	Approved
0.6119	Remote Similarity	NPD8299	Approved
0.6119	Remote Similarity	NPD8341	Approved
0.6111	Remote Similarity	NPD4634	Approved
0.6107	Remote Similarity	NPD7100	Approved
0.6107	Remote Similarity	NPD7101	Approved
0.6106	Remote Similarity	NPD3618	Phase 1
0.6106	Remote Similarity	NPD4249	Approved
0.609	Remote Similarity	NPD5126	Approved
0.609	Remote Similarity	NPD5125	Phase 3
0.6087	Remote Similarity	NPD5328	Approved
0.6068	Remote Similarity	NPD8171	Discontinued
0.6066	Remote Similarity	NPD4633	Approved
0.6066	Remote Similarity	NPD5224	Approved
0.6066	Remote Similarity	NPD5225	Approved
0.6066	Remote Similarity	NPD5226	Approved
0.6063	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6053	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.605	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.605	Remote Similarity	NPD5222	Approved
0.605	Remote Similarity	NPD5221	Approved
0.6048	Remote Similarity	NPD6640	Phase 3
0.6043	Remote Similarity	NPD8338	Approved
0.6043	Remote Similarity	NPD8449	Approved
0.6031	Remote Similarity	NPD6335	Approved
0.6019	Remote Similarity	NPD6932	Approved
0.6018	Remote Similarity	NPD1696	Phase 3
0.6018	Remote Similarity	NPD6893	Approved
0.6016	Remote Similarity	NPD5174	Approved
0.6016	Remote Similarity	NPD5175	Approved
0.6015	Remote Similarity	NPD6921	Approved
0.6014	Remote Similarity	NPD8392	Approved
0.6014	Remote Similarity	NPD8390	Approved
0.6014	Remote Similarity	NPD8391	Approved
0.6014	Remote Similarity	NPD5956	Approved
0.6	Remote Similarity	NPD5952	Clinical (unspecified phase)
0.6	Remote Similarity	NPD6274	Approved
0.6	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.6	Remote Similarity	NPD5173	Approved
0.6	Remote Similarity	NPD6868	Approved
0.6	Remote Similarity	NPD8450	Suspended
0.6	Remote Similarity	NPD4755	Approved
0.6	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.5984	Remote Similarity	NPD4159	Approved
0.5984	Remote Similarity	NPD5223	Approved
0.5983	Remote Similarity	NPD8035	Phase 2

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