NPASS Compound

Structure

CID218158 OpenBabel06191716012D 37 39 0 0 1 0 0 0 0 0999 V2000 6.7611 2.7444 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2051 3.9806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7861 1.0556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5164 3.0056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7055 -0.4069 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7014 -0.5584 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0195 -2.4772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3486 1.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7861 2.7444 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3608 4.4681 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3236 1.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8361 1.0556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0167 -0.4069 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3280 2.5181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0167 2.5181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2986 1.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5164 3.9806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8611 0.0806 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0027 0.3689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9732 -2.2745 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1724 3.0056 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3280 1.5431 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0167 1.5431 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1724 0.0806 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3280 4.4681 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3966 0.8907 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9697 0.1019 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.8611 1.0556 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1724 1.0556 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9564 0.5716 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6256 -2.9991 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3280 -0.4069 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3280 5.4431 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3503 1.0934 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2745 -1.3472 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1724 3.9806 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 16 1 0 0 0 0 4 17 1 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 16 1 0 0 0 0 10 17 2 0 0 0 0 11 12 1 0 0 0 0 11 16 2 0 0 0 0 12 28 1 0 0 0 0 13 18 1 0 0 0 0 13 24 1 0 0 0 0 14 21 1 0 0 0 0 14 22 1 0 0 0 0 15 21 1 0 0 0 0 15 23 1 0 0 0 0 17 25 1 0 0 0 0 18 28 1 1 0 0 0 19 30 2 0 0 0 0 19 34 1 0 0 0 0 20 31 2 0 0 0 0 20 35 1 0 0 0 0 21 36 1 6 0 0 0 22 26 1 0 0 0 0 22 29 1 1 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 32 1 0 0 0 0 25 33 2 0 0 0 0 25 36 1 0 0 0 0 26 34 1 1 0 0 0 26 37 1 0 0 0 0 27 29 1 0 0 0 0 27 35 1 0 0 0 0 27 37 1 0 0 0 0 28 8 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	518.29
Volume:	538.974
LogP:	3.013
LogD:	1.931
LogS:	-4.199
# Rotatable Bonds:	10
TPSA:	108.36
# H-Bond Aceptor:	8
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.225
Synthetic Accessibility Score:	5.9
Fsp3:	0.69
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:	-4.739
MDCK Permeability:	8.206750499084592e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.102
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.011
30% Bioavailability (F30%):	0.909

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.133
Plasma Protein Binding (PPB):	79.1332778930664%
Volume Distribution (VD):	2.454
Pgp-substrate:	18.750507354736328%

ADMET: Metabolism

CYP1A2-inhibitor:	0.033
CYP1A2-substrate:	0.057
CYP2C19-inhibitor:	0.043
CYP2C19-substrate:	0.729
CYP2C9-inhibitor:	0.31
CYP2C9-substrate:	0.087
CYP2D6-inhibitor:	0.036
CYP2D6-substrate:	0.099
CYP3A4-inhibitor:	0.75
CYP3A4-substrate:	0.363

ADMET: Excretion

Clearance (CL):	3.54
Half-life (T1/2):	0.503

ADMET: Toxicity

hERG Blockers:	0.058
Human Hepatotoxicity (H-HT):	0.865
Drug-inuced Liver Injury (DILI):	0.394
AMES Toxicity:	0.78
Rat Oral Acute Toxicity:	0.14
Maximum Recommended Daily Dose:	0.959
Skin Sensitization:	0.95
Carcinogencity:	0.101
Eye Corrosion:	0.502
Eye Irritation:	0.481
Respiratory Toxicity:	0.966

Download Data

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

Natural Product: NPC218158

Natural Product ID:	NPC218158
*Common Name:**	Casearinol A
IUPAC Name:	[(3S,3aS,5R,6aR,7S,8S,10R,10aR)-1,3-diacetyloxy-10-hydroxy-7,8-dimethyl-7-[(2E)-3-methylpenta-2,4-dienyl]-1,3,3a,4,5,6,6a,8,9,10-decahydrobenzo[d][2]benzofuran-5-yl] (E)-2-methylbut-2-enoate
Synonyms:
Standard InCHIKey:	GOBFDVWAFVUYAI-ZMMQRZHBSA-N
Standard InCHI:	InChI=1S/C29H42O8/c1-9-16(3)11-12-28(8)18(5)13-24(32)29-22(26(34-19(6)30)37-27(29)35-20(7)31)14-21(15-23(28)29)36-25(33)17(4)10-2/h9-11,18,21-24,26-27,32H,1,12-15H2,2-8H3/b16-11+,17-10+/t18-,21-,22+,23+,24+,26+,27?,28-,29-/m0/s1
SMILES:	C=C/C(=C/C[C@@]1(C)[C@@H](C)C[C@H]([C@]23[C@@H]1C[C@@H](OC(=O)/C(=C/C)/C)C[C@@H]3[C@@H](OC2OC(=O)C)OC(=O)C)O)/C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL458844
PubChem CID:	44559423
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
NPO14375	Casearia guianensis	Species	Salicaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[9322361]
NPO14375	Casearia guianensis	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14375	Casearia guianensis	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	1

Activity Type	# Activity
Protein Complex	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3964	Protein Complex	Intercellular adhesion molecule (ICAM-1), Integrin alpha-L/beta-2	Homo sapiens	IC50	=	50000.0	nM	PMID[524647]

☑ 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 NPC218158 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	191
0.1-0.2	1043
0.2-0.3	3806
0.3-0.4	7170
0.4-0.5	13439
0.5-0.6	7833
0.6-0.7	6232
0.7-0.8	2716
0.8-0.85	163
0.85-0.9	71
0.9-0.95	32
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.95	High Similarity	NPC109376
0.9406	High Similarity	NPC224660
0.9406	High Similarity	NPC470024
0.94	High Similarity	NPC172867
0.93	High Similarity	NPC264867
0.93	High Similarity	NPC201880
0.93	High Similarity	NPC470321
0.93	High Similarity	NPC473207
0.93	High Similarity	NPC81567
0.9223	High Similarity	NPC316708
0.92	High Similarity	NPC475889
0.92	High Similarity	NPC134270
0.92	High Similarity	NPC7613
0.92	High Similarity	NPC7644
0.92	High Similarity	NPC127933
0.9135	High Similarity	NPC470026
0.9135	High Similarity	NPC17791
0.9118	High Similarity	NPC184512
0.91	High Similarity	NPC238397
0.91	High Similarity	NPC471363
0.9048	High Similarity	NPC317460
0.9048	High Similarity	NPC328074
0.9048	High Similarity	NPC321272
0.9048	High Similarity	NPC470025
0.9029	High Similarity	NPC311223
0.902	High Similarity	NPC252296
0.899	High Similarity	NPC474440
0.8962	High Similarity	NPC470027
0.8942	High Similarity	NPC316974
0.8932	High Similarity	NPC88013
0.8932	High Similarity	NPC125423
0.8932	High Similarity	NPC475074
0.89	High Similarity	NPC473204
0.8857	High Similarity	NPC119550
0.8846	High Similarity	NPC217921
0.8846	High Similarity	NPC128795
0.8846	High Similarity	NPC135015
0.8846	High Similarity	NPC48548
0.8824	High Similarity	NPC120009
0.88	High Similarity	NPC472186
0.88	High Similarity	NPC476800
0.88	High Similarity	NPC473154
0.88	High Similarity	NPC318917
0.88	High Similarity	NPC471366
0.8788	High Similarity	NPC171598
0.8762	High Similarity	NPC40728
0.8713	High Similarity	NPC473545
0.8713	High Similarity	NPC324841
0.8713	High Similarity	NPC472187
0.87	High Similarity	NPC98112
0.87	High Similarity	NPC472188
0.8687	High Similarity	NPC471362
0.8687	High Similarity	NPC471372
0.8687	High Similarity	NPC472189
0.8654	High Similarity	NPC82251
0.8654	High Similarity	NPC239961
0.8641	High Similarity	NPC45897
0.8627	High Similarity	NPC198992
0.8611	High Similarity	NPC264153
0.8585	High Similarity	NPC206618
0.8544	High Similarity	NPC475038
0.8544	High Similarity	NPC109195
0.8544	High Similarity	NPC121423
0.8529	High Similarity	NPC20113
0.8529	High Similarity	NPC477972
0.8529	High Similarity	NPC228251
0.8529	High Similarity	NPC219285
0.8529	High Similarity	NPC161527
0.8529	High Similarity	NPC477968
0.8529	High Similarity	NPC477971
0.8505	High Similarity	NPC177047
0.85	High Similarity	NPC13924
0.8491	Intermediate Similarity	NPC38948
0.8485	Intermediate Similarity	NPC205034
0.8485	Intermediate Similarity	NPC152778
0.8485	Intermediate Similarity	NPC162615
0.8482	Intermediate Similarity	NPC257610
0.8469	Intermediate Similarity	NPC471370
0.8469	Intermediate Similarity	NPC471371
0.8468	Intermediate Similarity	NPC473828
0.8468	Intermediate Similarity	NPC473617
0.8462	Intermediate Similarity	NPC281378
0.8454	Intermediate Similarity	NPC263079
0.8447	Intermediate Similarity	NPC477717
0.844	Intermediate Similarity	NPC473159
0.844	Intermediate Similarity	NPC157441
0.8431	Intermediate Similarity	NPC278673
0.8416	Intermediate Similarity	NPC16967
0.84	Intermediate Similarity	NPC88507
0.84	Intermediate Similarity	NPC470255
0.84	Intermediate Similarity	NPC105490
0.8393	Intermediate Similarity	NPC470914
0.8381	Intermediate Similarity	NPC471937
0.8378	Intermediate Similarity	NPC474483
0.8365	Intermediate Similarity	NPC470571
0.8365	Intermediate Similarity	NPC472815
0.835	Intermediate Similarity	NPC477716
0.835	Intermediate Similarity	NPC477721
0.8349	Intermediate Similarity	NPC12046
0.8349	Intermediate Similarity	NPC194951
0.8333	Intermediate Similarity	NPC471082
0.8318	Intermediate Similarity	NPC392
0.8318	Intermediate Similarity	NPC177524
0.8318	Intermediate Similarity	NPC219900
0.8317	Intermediate Similarity	NPC276110
0.8302	Intermediate Similarity	NPC51719
0.83	Intermediate Similarity	NPC472640
0.83	Intermediate Similarity	NPC472641
0.83	Intermediate Similarity	NPC7349
0.83	Intermediate Similarity	NPC472812
0.8288	Intermediate Similarity	NPC471816
0.8286	Intermediate Similarity	NPC471938
0.8286	Intermediate Similarity	NPC471450
0.8283	Intermediate Similarity	NPC310479
0.8269	Intermediate Similarity	NPC11974
0.8235	Intermediate Similarity	NPC94905
0.8235	Intermediate Similarity	NPC8954
0.8235	Intermediate Similarity	NPC311166
0.8235	Intermediate Similarity	NPC165632
0.8235	Intermediate Similarity	NPC209297
0.8235	Intermediate Similarity	NPC475380
0.8224	Intermediate Similarity	NPC471205
0.8218	Intermediate Similarity	NPC57117
0.8218	Intermediate Similarity	NPC191521
0.82	Intermediate Similarity	NPC472811
0.82	Intermediate Similarity	NPC72845
0.8198	Intermediate Similarity	NPC475163
0.819	Intermediate Similarity	NPC471914
0.819	Intermediate Similarity	NPC150463
0.819	Intermediate Similarity	NPC471889
0.8182	Intermediate Similarity	NPC470819
0.8182	Intermediate Similarity	NPC473125
0.8173	Intermediate Similarity	NPC47024
0.8173	Intermediate Similarity	NPC16601
0.8158	Intermediate Similarity	NPC470312
0.8158	Intermediate Similarity	NPC135369
0.8158	Intermediate Similarity	NPC476150
0.8158	Intermediate Similarity	NPC476127
0.8155	Intermediate Similarity	NPC51499
0.8155	Intermediate Similarity	NPC477719
0.8155	Intermediate Similarity	NPC311241
0.8155	Intermediate Similarity	NPC475446
0.8155	Intermediate Similarity	NPC477718
0.8142	Intermediate Similarity	NPC470515
0.8137	Intermediate Similarity	NPC472441
0.8137	Intermediate Similarity	NPC135224
0.8137	Intermediate Similarity	NPC100892
0.8137	Intermediate Similarity	NPC477970
0.8137	Intermediate Similarity	NPC477969
0.8131	Intermediate Similarity	NPC34768
0.8125	Intermediate Similarity	NPC99620
0.8125	Intermediate Similarity	NPC5311
0.8125	Intermediate Similarity	NPC207637
0.8125	Intermediate Similarity	NPC310341
0.8125	Intermediate Similarity	NPC199428
0.8125	Intermediate Similarity	NPC193382
0.8113	Intermediate Similarity	NPC471887
0.8113	Intermediate Similarity	NPC132395
0.8113	Intermediate Similarity	NPC471888
0.8113	Intermediate Similarity	NPC471365
0.8113	Intermediate Similarity	NPC471886
0.8113	Intermediate Similarity	NPC474575
0.8113	Intermediate Similarity	NPC471885
0.8113	Intermediate Similarity	NPC23584
0.8113	Intermediate Similarity	NPC471364
0.8108	Intermediate Similarity	NPC290608
0.8108	Intermediate Similarity	NPC40133
0.8108	Intermediate Similarity	NPC44298
0.8108	Intermediate Similarity	NPC49413
0.8108	Intermediate Similarity	NPC473128
0.8103	Intermediate Similarity	NPC41129
0.81	Intermediate Similarity	NPC469403
0.81	Intermediate Similarity	NPC472642
0.81	Intermediate Similarity	NPC470817
0.81	Intermediate Similarity	NPC78973
0.81	Intermediate Similarity	NPC182136
0.8095	Intermediate Similarity	NPC280991
0.8095	Intermediate Similarity	NPC471412
0.8081	Intermediate Similarity	NPC472809
0.8081	Intermediate Similarity	NPC472810
0.8077	Intermediate Similarity	NPC107806
0.8077	Intermediate Similarity	NPC57079
0.8077	Intermediate Similarity	NPC108368
0.8077	Intermediate Similarity	NPC325229
0.8077	Intermediate Similarity	NPC275086
0.8077	Intermediate Similarity	NPC72647
0.8073	Intermediate Similarity	NPC322912
0.8073	Intermediate Similarity	NPC476759
0.8073	Intermediate Similarity	NPC112457
0.807	Intermediate Similarity	NPC470915
0.807	Intermediate Similarity	NPC268326
0.807	Intermediate Similarity	NPC153085
0.807	Intermediate Similarity	NPC470911
0.807	Intermediate Similarity	NPC470517
0.8061	Intermediate Similarity	NPC131813
0.8058	Intermediate Similarity	NPC134072
0.8058	Intermediate Similarity	NPC234993
0.8058	Intermediate Similarity	NPC473153
0.8056	Intermediate Similarity	NPC122816
0.8056	Intermediate Similarity	NPC302788

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 NPC218158 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	161
0.1-0.2	1156
0.2-0.3	3658
0.3-0.4	2681
0.4-0.5	961
0.5-0.6	266
0.6-0.7	210
0.7-0.8	53
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8318	Intermediate Similarity	NPD6686	Approved
0.8246	Intermediate Similarity	NPD7503	Approved
0.8077	Intermediate Similarity	NPD7638	Approved
0.8	Intermediate Similarity	NPD7640	Approved
0.8	Intermediate Similarity	NPD7639	Approved
0.7982	Intermediate Similarity	NPD7327	Approved
0.7982	Intermediate Similarity	NPD7328	Approved
0.7913	Intermediate Similarity	NPD7516	Approved
0.7845	Intermediate Similarity	NPD8294	Approved
0.7845	Intermediate Similarity	NPD8377	Approved
0.7778	Intermediate Similarity	NPD8033	Approved
0.7778	Intermediate Similarity	NPD8335	Approved
0.7778	Intermediate Similarity	NPD8380	Approved
0.7778	Intermediate Similarity	NPD8379	Approved
0.7778	Intermediate Similarity	NPD8378	Approved
0.7778	Intermediate Similarity	NPD8296	Approved
0.7736	Intermediate Similarity	NPD4225	Approved
0.7667	Intermediate Similarity	NPD7507	Approved
0.748	Intermediate Similarity	NPD7319	Approved
0.7407	Intermediate Similarity	NPD8029	Clinical (unspecified phase)
0.7404	Intermediate Similarity	NPD7838	Discovery
0.7391	Intermediate Similarity	NPD6882	Approved
0.7364	Intermediate Similarity	NPD7632	Discontinued
0.7339	Intermediate Similarity	NPD6648	Approved
0.7273	Intermediate Similarity	NPD6370	Approved
0.7273	Intermediate Similarity	NPD5344	Discontinued
0.7258	Intermediate Similarity	NPD7736	Approved
0.7257	Intermediate Similarity	NPD6412	Phase 2
0.719	Intermediate Similarity	NPD8517	Approved
0.719	Intermediate Similarity	NPD8513	Phase 3
0.719	Intermediate Similarity	NPD8516	Approved
0.719	Intermediate Similarity	NPD8515	Approved
0.7179	Intermediate Similarity	NPD8133	Approved
0.717	Intermediate Similarity	NPD7637	Suspended
0.7157	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.7154	Intermediate Similarity	NPD7492	Approved
0.713	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.713	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7107	Intermediate Similarity	NPD6054	Approved
0.7097	Intermediate Similarity	NPD6616	Approved
0.7073	Intermediate Similarity	NPD8328	Phase 3
0.7069	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD6881	Approved
0.7043	Intermediate Similarity	NPD6899	Approved
0.704	Intermediate Similarity	NPD7078	Approved
0.704	Intermediate Similarity	NPD8293	Discontinued
0.7009	Intermediate Similarity	NPD6649	Approved
0.7009	Intermediate Similarity	NPD6650	Approved
0.7	Intermediate Similarity	NPD6009	Approved
0.7	Intermediate Similarity	NPD7115	Discovery
0.6961	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6957	Remote Similarity	NPD5697	Approved
0.6949	Remote Similarity	NPD8297	Approved
0.6923	Remote Similarity	NPD7102	Approved
0.6923	Remote Similarity	NPD6883	Approved
0.6923	Remote Similarity	NPD1694	Approved
0.6923	Remote Similarity	NPD7290	Approved
0.6911	Remote Similarity	NPD6016	Approved
0.6911	Remote Similarity	NPD6015	Approved
0.6881	Remote Similarity	NPD7748	Approved
0.687	Remote Similarity	NPD6675	Approved
0.687	Remote Similarity	NPD6402	Approved
0.687	Remote Similarity	NPD5739	Approved
0.687	Remote Similarity	NPD7128	Approved
0.6864	Remote Similarity	NPD6847	Approved
0.6864	Remote Similarity	NPD8130	Phase 1
0.6864	Remote Similarity	NPD6617	Approved
0.6864	Remote Similarity	NPD6869	Approved
0.6855	Remote Similarity	NPD5988	Approved
0.6852	Remote Similarity	NPD7515	Phase 2
0.6847	Remote Similarity	NPD7902	Approved
0.6838	Remote Similarity	NPD6014	Approved
0.6838	Remote Similarity	NPD6012	Approved
0.6838	Remote Similarity	NPD6373	Approved
0.6838	Remote Similarity	NPD6372	Approved
0.6838	Remote Similarity	NPD6013	Approved
0.6829	Remote Similarity	NPD6059	Approved
0.6829	Remote Similarity	NPD6319	Approved
0.6827	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.681	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.68	Remote Similarity	NPD6067	Discontinued
0.6789	Remote Similarity	NPD5779	Approved
0.6789	Remote Similarity	NPD5778	Approved
0.6759	Remote Similarity	NPD46	Approved
0.6759	Remote Similarity	NPD6698	Approved
0.6752	Remote Similarity	NPD7320	Approved
0.6752	Remote Similarity	NPD6011	Approved
0.675	Remote Similarity	NPD4632	Approved
0.6731	Remote Similarity	NPD6695	Phase 3
0.6721	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6697	Remote Similarity	NPD6079	Approved
0.6667	Remote Similarity	NPD5701	Approved
0.6641	Remote Similarity	NPD8074	Phase 3
0.6636	Remote Similarity	NPD6399	Phase 3
0.661	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD5211	Phase 2
0.6602	Remote Similarity	NPD7525	Registered
0.6583	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6581	Remote Similarity	NPD6008	Approved
0.6579	Remote Similarity	NPD5286	Approved
0.6579	Remote Similarity	NPD5285	Approved
0.6579	Remote Similarity	NPD4696	Approved
0.6577	Remote Similarity	NPD7900	Approved
0.6577	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6549	Remote Similarity	NPD6083	Phase 2
0.6549	Remote Similarity	NPD6084	Phase 2
0.6545	Remote Similarity	NPD6411	Approved
0.6542	Remote Similarity	NPD3618	Phase 1
0.6535	Remote Similarity	NPD7604	Phase 2
0.6529	Remote Similarity	NPD6053	Discontinued
0.6518	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6514	Remote Similarity	NPD6051	Approved
0.6514	Remote Similarity	NPD5328	Approved
0.6508	Remote Similarity	NPD5983	Phase 2
0.6505	Remote Similarity	NPD6929	Approved
0.6505	Remote Similarity	NPD7645	Phase 2
0.6496	Remote Similarity	NPD5141	Approved
0.6481	Remote Similarity	NPD7750	Discontinued
0.6481	Remote Similarity	NPD7524	Approved
0.648	Remote Similarity	NPD7101	Approved
0.648	Remote Similarity	NPD7100	Approved
0.6466	Remote Similarity	NPD5225	Approved
0.6466	Remote Similarity	NPD5224	Approved
0.6466	Remote Similarity	NPD4633	Approved
0.6466	Remote Similarity	NPD5226	Approved
0.646	Remote Similarity	NPD5221	Approved
0.646	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.646	Remote Similarity	NPD5222	Approved
0.6446	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6442	Remote Similarity	NPD7514	Phase 3
0.6442	Remote Similarity	NPD6930	Phase 2
0.6442	Remote Similarity	NPD6931	Approved
0.6442	Remote Similarity	NPD7332	Phase 2
0.6439	Remote Similarity	NPD7260	Phase 2
0.6434	Remote Similarity	NPD6336	Discontinued
0.641	Remote Similarity	NPD5175	Approved
0.641	Remote Similarity	NPD5174	Approved
0.6408	Remote Similarity	NPD7145	Approved
0.6406	Remote Similarity	NPD7829	Approved
0.6406	Remote Similarity	NPD7830	Approved
0.6404	Remote Similarity	NPD5173	Approved
0.6404	Remote Similarity	NPD4755	Approved
0.64	Remote Similarity	NPD6335	Approved
0.6396	Remote Similarity	NPD8034	Phase 2
0.6396	Remote Similarity	NPD8035	Phase 2
0.6396	Remote Similarity	NPD7983	Approved
0.6389	Remote Similarity	NPD7521	Approved
0.6389	Remote Similarity	NPD7334	Approved
0.6389	Remote Similarity	NPD6684	Approved
0.6389	Remote Similarity	NPD6409	Approved
0.6389	Remote Similarity	NPD7146	Approved
0.6389	Remote Similarity	NPD5330	Approved
0.6387	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6383	Remote Similarity	NPD7625	Phase 1
0.6381	Remote Similarity	NPD6902	Approved
0.6379	Remote Similarity	NPD5223	Approved
0.6371	Remote Similarity	NPD6274	Approved
0.6371	Remote Similarity	NPD6868	Approved
0.6364	Remote Similarity	NPD6371	Approved
0.6364	Remote Similarity	NPD4634	Approved
0.6364	Remote Similarity	NPD6101	Approved
0.6364	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6339	Remote Similarity	NPD4202	Approved
0.6336	Remote Similarity	NPD6033	Approved
0.6333	Remote Similarity	NPD4730	Approved
0.6333	Remote Similarity	NPD4729	Approved
0.633	Remote Similarity	NPD4250	Approved
0.633	Remote Similarity	NPD3573	Approved
0.633	Remote Similarity	NPD4251	Approved
0.6324	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6321	Remote Similarity	NPD5209	Approved
0.632	Remote Similarity	NPD6317	Approved
0.6316	Remote Similarity	NPD7839	Suspended
0.6311	Remote Similarity	NPD6932	Approved
0.6311	Remote Similarity	NPD5776	Phase 2
0.6311	Remote Similarity	NPD6925	Approved
0.6306	Remote Similarity	NPD5785	Approved
0.6296	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6293	Remote Similarity	NPD4700	Approved
0.6275	Remote Similarity	NPD8264	Approved
0.6273	Remote Similarity	NPD6672	Approved
0.6273	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6273	Remote Similarity	NPD5737	Approved
0.6273	Remote Similarity	NPD6903	Approved
0.627	Remote Similarity	NPD6313	Approved
0.627	Remote Similarity	NPD6314	Approved
0.625	Remote Similarity	NPD5284	Approved
0.625	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.625	Remote Similarity	NPD7087	Discontinued
0.625	Remote Similarity	NPD5281	Approved
0.6239	Remote Similarity	NPD4249	Approved
0.623	Remote Similarity	NPD5251	Approved
0.623	Remote Similarity	NPD5250	Approved
0.623	Remote Similarity	NPD5247	Approved
0.623	Remote Similarity	NPD5248	Approved
0.623	Remote Similarity	NPD5249	Phase 3
0.6228	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6228	Remote Similarity	NPD5695	Phase 3
0.6207	Remote Similarity	NPD5696	Approved
0.6204	Remote Similarity	NPD4786	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