NPASS Compound

Structure

NPC128795 OpenBabel07101719252D 41 43 0 0 1 0 0 0 0 0999 V2000 -6.9345 1.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2617 4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3956 5.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9345 2.8147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8005 -0.4173 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8005 -1.4173 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7450 -0.5727 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0238 -2.3328 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4345 1.9487 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9345 1.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4345 1.9487 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9345 1.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5296 4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3364 2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0685 2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3956 4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4345 1.9487 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9345 0.0827 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9345 -1.9173 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0540 0.3783 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3546 -1.5897 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2024 3.0827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3364 1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0685 1.5827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3364 4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0685 -0.4173 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2024 0.0827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4067 0.9135 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9945 0.1045 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9345 1.0827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2024 1.0827 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9345 -2.9173 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0322 0.5862 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3765 -1.7976 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3364 5.5827 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3364 -0.4173 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0685 -1.4173 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3849 1.1215 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6637 -0.6386 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2024 4.0827 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 16 1 0 0 0 0 3 16 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 8 21 1 0 0 0 0 10 17 1 0 0 0 0 11 12 1 0 0 0 0 11 17 1 0 0 0 0 12 30 1 0 0 0 0 13 16 1 0 0 0 0 13 25 1 0 0 0 0 14 22 1 0 0 0 0 14 23 2 0 0 0 0 15 22 1 0 0 0 0 15 24 1 0 0 0 0 18 26 1 0 0 0 0 18 30 1 6 0 0 0 19 32 2 0 0 0 0 19 37 1 0 0 0 0 20 33 2 0 0 0 0 20 38 1 0 0 0 0 21 34 2 0 0 0 0 21 39 1 0 0 0 0 22 40 1 6 0 0 0 23 28 1 0 0 0 0 24 30 1 1 0 0 0 24 31 1 0 0 0 0 25 35 2 0 0 0 0 25 40 1 0 0 0 0 26 27 1 0 0 0 0 26 37 1 6 0 0 0 27 31 1 6 0 0 0 27 36 1 0 0 0 0 28 38 1 6 0 0 0 28 41 1 0 0 0 0 29 31 1 6 0 0 0 29 39 1 0 0 0 0 29 41 1 0 0 0 0 30 9 1 1 0 0 0 31 23 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	576.29
Volume:	588.51
LogP:	3.676
LogD:	2.883
LogS:	-4.455
# Rotatable Bonds:	14
TPSA:	134.66
# H-Bond Aceptor:	10
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.175
Synthetic Accessibility Score:	5.91
Fsp3:	0.677
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:	-4.914
MDCK Permeability:	8.518192043993622e-05
Pgp-inhibitor:	0.994
Pgp-substrate:	0.008
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.628

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.102
Plasma Protein Binding (PPB):	76.4067611694336%
Volume Distribution (VD):	1.764
Pgp-substrate:	23.493789672851562%

ADMET: Metabolism

CYP1A2-inhibitor:	0.026
CYP1A2-substrate:	0.022
CYP2C19-inhibitor:	0.014
CYP2C19-substrate:	0.093
CYP2C9-inhibitor:	0.204
CYP2C9-substrate:	0.052
CYP2D6-inhibitor:	0.035
CYP2D6-substrate:	0.078
CYP3A4-inhibitor:	0.416
CYP3A4-substrate:	0.322

ADMET: Excretion

Clearance (CL):	2.603
Half-life (T1/2):	0.436

ADMET: Toxicity

hERG Blockers:	0.096
Human Hepatotoxicity (H-HT):	0.97
Drug-inuced Liver Injury (DILI):	0.977
AMES Toxicity:	0.794
Rat Oral Acute Toxicity:	0.844
Maximum Recommended Daily Dose:	0.972
Skin Sensitization:	0.841
Carcinogencity:	0.067
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.96

Download Data

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

Natural Product: NPC128795

Natural Product ID:	NPC128795
*Common Name:**	Caseamembrin O
IUPAC Name:	[(1R,3S,5S,6aR,7R,8R,9R,10S,10aR)-1,3,9-triacetyloxy-10-hydroxy-7,8-dimethyl-7-(3-methylidenepent-4-enyl)-1,3,5,6,6a,8,9,10-octahydrobenzo[d][2]benzofuran-5-yl] 3-methylbutanoate
Synonyms:	caseamembrin O
Standard InCHIKey:	MXZZEEMZKQYYNV-PCCLTOHNSA-N
Standard InCHI:	InChI=1S/C31H44O10/c1-10-17(4)11-12-30(9)18(5)26(37-19(6)32)27(36)31-23(28(38-20(7)33)41-29(31)39-21(8)34)14-22(15-24(30)31)40-25(35)13-16(2)3/h10,14,16,18,22,24,26-29,36H,1,4,11-13,15H2,2-3,5-9H3/t18-,22+,24+,26+,27+,28+,29-,30-,31-/m0/s1
SMILES:	C=CC(=C)CC[C@@]1(C)[C@@H](C)[C@H]([C@H]([C@]23C(=C[C@H](C[C@H]12)OC(=O)CC(C)C)[C@H](OC(=O)C)O[C@@H]3OC(=O)C)O)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL464951
PubChem CID:	6326337
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
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	twig	n.a.	PMID[14709876]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[14709876]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	Leaves; Twigs	n.a.	n.a.	PMID[15043402]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16309320]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24498	Casearia membranacea	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24498	Casearia membranacea	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
ED50	3

Activity Type	# Activity
Cell Line	2
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT579	Cell Line	DLD-1	Homo sapiens	ED50	=	2.54	ug ml-1	PMID[549065]
NPT91	Cell Line	KB	Homo sapiens	ED50	=	6.94	ug ml-1	PMID[549065]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	1.94	ug ml-1	PMID[549065]

☑ 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 NPC128795 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	195
0.1-0.2	1099
0.2-0.3	3910
0.3-0.4	7228
0.4-0.5	12892
0.5-0.6	8208
0.6-0.7	5997
0.7-0.8	2922
0.8-0.85	150
0.85-0.9	25
0.9-0.95	47
0.95-1	24

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC217921
1.0	High Similarity	NPC48548
1.0	High Similarity	NPC135015
0.99	High Similarity	NPC40728
0.99	High Similarity	NPC316974
0.9899	High Similarity	NPC125423
0.9899	High Similarity	NPC88013
0.98	High Similarity	NPC311223
0.9608	High Similarity	NPC119550
0.9596	High Similarity	NPC7644
0.9596	High Similarity	NPC127933
0.9596	High Similarity	NPC475889
0.9596	High Similarity	NPC7613
0.95	High Similarity	NPC264867
0.95	High Similarity	NPC201880
0.95	High Similarity	NPC81567
0.95	High Similarity	NPC473207
0.95	High Similarity	NPC470321
0.9495	High Similarity	NPC471363
0.9495	High Similarity	NPC238397
0.94	High Similarity	NPC134270
0.9314	High Similarity	NPC184512
0.9238	High Similarity	NPC317460
0.9238	High Similarity	NPC328074
0.9238	High Similarity	NPC321272
0.9238	High Similarity	NPC470025
0.9231	High Similarity	NPC316708
0.9216	High Similarity	NPC252296
0.9192	High Similarity	NPC471366
0.9192	High Similarity	NPC476800
0.9192	High Similarity	NPC472186
0.9192	High Similarity	NPC318917
0.9151	High Similarity	NPC470027
0.9143	High Similarity	NPC17791
0.9143	High Similarity	NPC470026
0.91	High Similarity	NPC473545
0.91	High Similarity	NPC473204
0.91	High Similarity	NPC472187
0.9091	High Similarity	NPC472188
0.899	High Similarity	NPC171598
0.8942	High Similarity	NPC109376
0.8889	High Similarity	NPC471362
0.8889	High Similarity	NPC471372
0.8889	High Similarity	NPC472189
0.8857	High Similarity	NPC470024
0.8857	High Similarity	NPC224660
0.8846	High Similarity	NPC172867
0.8846	High Similarity	NPC218158
0.8762	High Similarity	NPC293512
0.8739	High Similarity	NPC122971
0.8713	High Similarity	NPC98112
0.8667	High Similarity	NPC82251
0.8667	High Similarity	NPC239961
0.8641	High Similarity	NPC280991
0.8641	High Similarity	NPC198992
0.8624	High Similarity	NPC474410
0.8624	High Similarity	NPC264153
0.8624	High Similarity	NPC293658
0.86	High Similarity	NPC88507
0.8598	High Similarity	NPC206618
0.8585	High Similarity	NPC472390
0.8571	High Similarity	NPC470914
0.8571	High Similarity	NPC470768
0.8558	High Similarity	NPC472552
0.8544	High Similarity	NPC477971
0.8544	High Similarity	NPC477972
0.8544	High Similarity	NPC219285
0.8544	High Similarity	NPC161527
0.8544	High Similarity	NPC228251
0.8544	High Similarity	NPC477968
0.8544	High Similarity	NPC20113
0.8532	High Similarity	NPC473125
0.8529	High Similarity	NPC91197
0.8529	High Similarity	NPC239547
0.8529	High Similarity	NPC155319
0.8529	High Similarity	NPC96597
0.8529	High Similarity	NPC309503
0.8529	High Similarity	NPC125551
0.8519	High Similarity	NPC177047
0.8519	High Similarity	NPC83005
0.8515	High Similarity	NPC286612
0.8515	High Similarity	NPC275310
0.8515	High Similarity	NPC230347
0.8505	High Similarity	NPC38948
0.8491	Intermediate Similarity	NPC470767
0.8491	Intermediate Similarity	NPC470763
0.8482	Intermediate Similarity	NPC473828
0.8482	Intermediate Similarity	NPC473617
0.8476	Intermediate Similarity	NPC23584
0.8476	Intermediate Similarity	NPC281378
0.8476	Intermediate Similarity	NPC474124
0.8462	Intermediate Similarity	NPC475617
0.8462	Intermediate Similarity	NPC472554
0.8455	Intermediate Similarity	NPC75167
0.8455	Intermediate Similarity	NPC49413
0.8455	Intermediate Similarity	NPC44298
0.8455	Intermediate Similarity	NPC311592
0.8455	Intermediate Similarity	NPC473128
0.8455	Intermediate Similarity	NPC40133
0.8455	Intermediate Similarity	NPC290608
0.8447	Intermediate Similarity	NPC477928
0.8435	Intermediate Similarity	NPC41129
0.8431	Intermediate Similarity	NPC311166
0.8407	Intermediate Similarity	NPC477071
0.8393	Intermediate Similarity	NPC473405
0.8393	Intermediate Similarity	NPC473968
0.8384	Intermediate Similarity	NPC470819
0.8381	Intermediate Similarity	NPC475344
0.8381	Intermediate Similarity	NPC121423
0.8381	Intermediate Similarity	NPC11956
0.8381	Intermediate Similarity	NPC470571
0.8381	Intermediate Similarity	NPC476471
0.8378	Intermediate Similarity	NPC181145
0.8365	Intermediate Similarity	NPC188968
0.8365	Intermediate Similarity	NPC272223
0.8319	Intermediate Similarity	NPC471548
0.8304	Intermediate Similarity	NPC207637
0.8304	Intermediate Similarity	NPC471816
0.8302	Intermediate Similarity	NPC120009
0.83	Intermediate Similarity	NPC471371
0.83	Intermediate Similarity	NPC471370
0.83	Intermediate Similarity	NPC470817
0.8288	Intermediate Similarity	NPC473159
0.8273	Intermediate Similarity	NPC263827
0.8273	Intermediate Similarity	NPC250481
0.8273	Intermediate Similarity	NPC285410
0.8269	Intermediate Similarity	NPC473154
0.8261	Intermediate Similarity	NPC476204
0.8261	Intermediate Similarity	NPC170084
0.8257	Intermediate Similarity	NPC143706
0.8257	Intermediate Similarity	NPC472534
0.8257	Intermediate Similarity	NPC257853
0.8252	Intermediate Similarity	NPC94905
0.8252	Intermediate Similarity	NPC221801
0.8252	Intermediate Similarity	NPC8954
0.8252	Intermediate Similarity	NPC284194
0.8252	Intermediate Similarity	NPC211810
0.8252	Intermediate Similarity	NPC471765
0.8246	Intermediate Similarity	NPC475775
0.8246	Intermediate Similarity	NPC476529
0.8241	Intermediate Similarity	NPC473586
0.8241	Intermediate Similarity	NPC33053
0.8235	Intermediate Similarity	NPC96736
0.8235	Intermediate Similarity	NPC178949
0.8235	Intermediate Similarity	NPC211238
0.8235	Intermediate Similarity	NPC472416
0.8235	Intermediate Similarity	NPC472360
0.823	Intermediate Similarity	NPC23046
0.823	Intermediate Similarity	NPC203862
0.823	Intermediate Similarity	NPC474483
0.8224	Intermediate Similarity	NPC473543
0.8224	Intermediate Similarity	NPC85593
0.8224	Intermediate Similarity	NPC31430
0.8224	Intermediate Similarity	NPC475585
0.8224	Intermediate Similarity	NPC222161
0.8224	Intermediate Similarity	NPC93352
0.8224	Intermediate Similarity	NPC474550
0.8224	Intermediate Similarity	NPC473577
0.822	Intermediate Similarity	NPC470780
0.8218	Intermediate Similarity	NPC477574
0.8214	Intermediate Similarity	NPC470919
0.8214	Intermediate Similarity	NPC472274
0.8214	Intermediate Similarity	NPC469877
0.8214	Intermediate Similarity	NPC220293
0.8214	Intermediate Similarity	NPC475163
0.8208	Intermediate Similarity	NPC201191
0.8208	Intermediate Similarity	NPC472815
0.8208	Intermediate Similarity	NPC154452
0.82	Intermediate Similarity	NPC246028
0.8198	Intermediate Similarity	NPC174836
0.8198	Intermediate Similarity	NPC212968
0.8198	Intermediate Similarity	NPC302146
0.8198	Intermediate Similarity	NPC116794
0.8198	Intermediate Similarity	NPC64106
0.8198	Intermediate Similarity	NPC125923
0.8198	Intermediate Similarity	NPC65590
0.8198	Intermediate Similarity	NPC231797
0.819	Intermediate Similarity	NPC64348
0.819	Intermediate Similarity	NPC471082
0.8182	Intermediate Similarity	NPC191439
0.8182	Intermediate Similarity	NPC102914
0.8182	Intermediate Similarity	NPC170974
0.8182	Intermediate Similarity	NPC103627
0.8182	Intermediate Similarity	NPC235014
0.8182	Intermediate Similarity	NPC129340
0.8182	Intermediate Similarity	NPC110139
0.8182	Intermediate Similarity	NPC101450
0.8182	Intermediate Similarity	NPC199457
0.8182	Intermediate Similarity	NPC108709
0.8182	Intermediate Similarity	NPC274507
0.8182	Intermediate Similarity	NPC220984
0.8182	Intermediate Similarity	NPC46407
0.8182	Intermediate Similarity	NPC75747
0.8182	Intermediate Similarity	NPC127153
0.8182	Intermediate Similarity	NPC68419
0.8182	Intermediate Similarity	NPC7870
0.8174	Intermediate Similarity	NPC107338
0.8174	Intermediate Similarity	NPC48692
0.8174	Intermediate Similarity	NPC109607
0.8173	Intermediate Similarity	NPC240372

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 NPC128795 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	164
0.1-0.2	1344
0.2-0.3	3662
0.3-0.4	2534
0.4-0.5	900
0.5-0.6	329
0.6-0.7	189
0.7-0.8	28
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
0.8165	Intermediate Similarity	NPD6686	Approved
0.7949	Intermediate Similarity	NPD7503	Approved
0.7931	Intermediate Similarity	NPD7516	Approved
0.7845	Intermediate Similarity	NPD7328	Approved
0.7845	Intermediate Similarity	NPD7327	Approved
0.7797	Intermediate Similarity	NPD8033	Approved
0.7797	Intermediate Similarity	NPD8517	Approved
0.7797	Intermediate Similarity	NPD8515	Approved
0.7797	Intermediate Similarity	NPD8513	Phase 3
0.7797	Intermediate Similarity	NPD8516	Approved
0.7768	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7757	Intermediate Similarity	NPD4225	Approved
0.7712	Intermediate Similarity	NPD8294	Approved
0.7712	Intermediate Similarity	NPD8377	Approved
0.7686	Intermediate Similarity	NPD7507	Approved
0.7647	Intermediate Similarity	NPD8296	Approved
0.7647	Intermediate Similarity	NPD8380	Approved
0.7647	Intermediate Similarity	NPD8335	Approved
0.7647	Intermediate Similarity	NPD8379	Approved
0.7647	Intermediate Similarity	NPD8378	Approved
0.7593	Intermediate Similarity	NPD7638	Approved
0.7523	Intermediate Similarity	NPD7640	Approved
0.7523	Intermediate Similarity	NPD7639	Approved
0.75	Intermediate Similarity	NPD7319	Approved
0.75	Intermediate Similarity	NPD8133	Approved
0.7456	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7455	Intermediate Similarity	NPD5344	Discontinued
0.7434	Intermediate Similarity	NPD6412	Phase 2
0.7311	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD8029	Clinical (unspecified phase)
0.7264	Intermediate Similarity	NPD7838	Discovery
0.7241	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7236	Intermediate Similarity	NPD8328	Phase 3
0.7207	Intermediate Similarity	NPD6648	Approved
0.72	Intermediate Similarity	NPD8074	Phase 3
0.7179	Intermediate Similarity	NPD8413	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD7115	Discovery
0.7154	Intermediate Similarity	NPD6370	Approved
0.7143	Intermediate Similarity	NPD7736	Approved
0.7103	Intermediate Similarity	NPD46	Approved
0.7103	Intermediate Similarity	NPD6698	Approved
0.7069	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD8293	Discontinued
0.704	Intermediate Similarity	NPD7492	Approved
0.7037	Intermediate Similarity	NPD7637	Suspended
0.7019	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.6992	Remote Similarity	NPD6054	Approved
0.6984	Remote Similarity	NPD6616	Approved
0.6983	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD6882	Approved
0.6972	Remote Similarity	NPD5779	Approved
0.6972	Remote Similarity	NPD5778	Approved
0.693	Remote Similarity	NPD7632	Discontinued
0.6929	Remote Similarity	NPD7078	Approved
0.6885	Remote Similarity	NPD6009	Approved
0.6881	Remote Similarity	NPD7983	Approved
0.6855	Remote Similarity	NPD6319	Approved
0.6855	Remote Similarity	NPD6059	Approved
0.6833	Remote Similarity	NPD8297	Approved
0.6825	Remote Similarity	NPD6067	Discontinued
0.6822	Remote Similarity	NPD7524	Approved
0.6818	Remote Similarity	NPD6399	Phase 3
0.68	Remote Similarity	NPD6015	Approved
0.68	Remote Similarity	NPD6016	Approved
0.6777	Remote Similarity	NPD4632	Approved
0.6746	Remote Similarity	NPD5988	Approved
0.6727	Remote Similarity	NPD6411	Approved
0.6639	Remote Similarity	NPD6881	Approved
0.6639	Remote Similarity	NPD6899	Approved
0.6636	Remote Similarity	NPD1694	Approved
0.6612	Remote Similarity	NPD6649	Approved
0.6612	Remote Similarity	NPD6650	Approved
0.661	Remote Similarity	NPD6675	Approved
0.661	Remote Similarity	NPD6402	Approved
0.661	Remote Similarity	NPD7128	Approved
0.661	Remote Similarity	NPD5739	Approved
0.6607	Remote Similarity	NPD7748	Approved
0.6583	Remote Similarity	NPD6372	Approved
0.6583	Remote Similarity	NPD6373	Approved
0.6579	Remote Similarity	NPD7902	Approved
0.6577	Remote Similarity	NPD7515	Phase 2
0.6557	Remote Similarity	NPD6053	Discontinued
0.6555	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6555	Remote Similarity	NPD5697	Approved
0.6545	Remote Similarity	NPD6101	Approved
0.6545	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6542	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD6921	Approved
0.6529	Remote Similarity	NPD6883	Approved
0.6529	Remote Similarity	NPD6371	Approved
0.6529	Remote Similarity	NPD7290	Approved
0.6529	Remote Similarity	NPD7102	Approved
0.6514	Remote Similarity	NPD4251	Approved
0.6514	Remote Similarity	NPD4250	Approved
0.65	Remote Similarity	NPD7320	Approved
0.6475	Remote Similarity	NPD6869	Approved
0.6475	Remote Similarity	NPD6617	Approved
0.6475	Remote Similarity	NPD6847	Approved
0.6475	Remote Similarity	NPD8130	Phase 1
0.6471	Remote Similarity	NPD6008	Approved
0.6466	Remote Similarity	NPD7260	Phase 2
0.6462	Remote Similarity	NPD8451	Approved
0.6449	Remote Similarity	NPD6695	Phase 3
0.6446	Remote Similarity	NPD6013	Approved
0.6446	Remote Similarity	NPD6014	Approved
0.6446	Remote Similarity	NPD6012	Approved
0.6434	Remote Similarity	NPD7604	Phase 2
0.6434	Remote Similarity	NPD7829	Approved
0.6434	Remote Similarity	NPD7830	Approved
0.6422	Remote Similarity	NPD4249	Approved
0.6417	Remote Similarity	NPD5701	Approved
0.6412	Remote Similarity	NPD8448	Approved
0.6408	Remote Similarity	NPD7625	Phase 1
0.6406	Remote Similarity	NPD8444	Approved
0.6406	Remote Similarity	NPD5983	Phase 2
0.6396	Remote Similarity	NPD6051	Approved
0.6389	Remote Similarity	NPD4786	Approved
0.6381	Remote Similarity	NPD7645	Phase 2
0.6364	Remote Similarity	NPD6033	Approved
0.6364	Remote Similarity	NPD6011	Approved
0.6355	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6355	Remote Similarity	NPD3667	Approved
0.6348	Remote Similarity	NPD7839	Suspended
0.6339	Remote Similarity	NPD3168	Discontinued
0.6336	Remote Similarity	NPD6336	Discontinued
0.6321	Remote Similarity	NPD7525	Registered
0.6321	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD7900	Approved
0.6311	Remote Similarity	NPD8264	Approved
0.6296	Remote Similarity	NPD3669	Approved
0.6296	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6293	Remote Similarity	NPD6083	Phase 2
0.6293	Remote Similarity	NPD6084	Phase 2
0.6283	Remote Similarity	NPD6079	Approved
0.6283	Remote Similarity	NPD8035	Phase 2
0.6283	Remote Similarity	NPD8034	Phase 2
0.6273	Remote Similarity	NPD3618	Phase 1
0.6271	Remote Similarity	NPD4159	Approved
0.6269	Remote Similarity	NPD8390	Approved
0.6269	Remote Similarity	NPD8391	Approved
0.6269	Remote Similarity	NPD8392	Approved
0.6261	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.626	Remote Similarity	NPD8299	Approved
0.626	Remote Similarity	NPD4634	Approved
0.626	Remote Similarity	NPD8342	Approved
0.626	Remote Similarity	NPD8341	Approved
0.626	Remote Similarity	NPD8340	Approved
0.625	Remote Similarity	NPD5328	Approved
0.625	Remote Similarity	NPD8170	Clinical (unspecified phase)
0.6238	Remote Similarity	NPD7532	Clinical (unspecified phase)
0.6232	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6231	Remote Similarity	NPD5126	Approved
0.6231	Remote Similarity	NPD5125	Phase 3
0.6228	Remote Similarity	NPD8171	Discontinued
0.6226	Remote Similarity	NPD6929	Approved
0.6218	Remote Similarity	NPD5211	Phase 2
0.6216	Remote Similarity	NPD7750	Discontinued
0.621	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6186	Remote Similarity	NPD5286	Approved
0.6186	Remote Similarity	NPD5285	Approved
0.6186	Remote Similarity	NPD4696	Approved
0.6182	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6182	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6176	Remote Similarity	NPD8449	Approved
0.6176	Remote Similarity	NPD6845	Suspended
0.6172	Remote Similarity	NPD7641	Discontinued
0.6168	Remote Similarity	NPD7514	Phase 3
0.6168	Remote Similarity	NPD4820	Approved
0.6168	Remote Similarity	NPD4819	Approved
0.6168	Remote Similarity	NPD7332	Phase 2
0.6168	Remote Similarity	NPD6931	Approved
0.6168	Remote Similarity	NPD6930	Phase 2
0.6168	Remote Similarity	NPD4821	Approved
0.6168	Remote Similarity	NPD4822	Approved
0.6154	Remote Similarity	NPD4755	Approved
0.6154	Remote Similarity	NPD7339	Approved
0.6154	Remote Similarity	NPD8039	Approved
0.6154	Remote Similarity	NPD6942	Approved
0.6147	Remote Similarity	NPD7154	Phase 3
0.6132	Remote Similarity	NPD4268	Approved
0.6132	Remote Similarity	NPD4271	Approved
0.6132	Remote Similarity	NPD7145	Approved
0.6131	Remote Similarity	NPD8450	Suspended
0.6126	Remote Similarity	NPD7146	Approved
0.6126	Remote Similarity	NPD7334	Approved
0.6126	Remote Similarity	NPD6409	Approved
0.6126	Remote Similarity	NPD5330	Approved
0.6126	Remote Similarity	NPD7521	Approved
0.6126	Remote Similarity	NPD6684	Approved
0.6124	Remote Similarity	NPD7100	Approved
0.6124	Remote Similarity	NPD7101	Approved
0.6121	Remote Similarity	NPD5695	Phase 3
0.6116	Remote Similarity	NPD5141	Approved
0.6111	Remote Similarity	NPD6902	Approved
0.6101	Remote Similarity	NPD7799	Discontinued
0.6095	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.6095	Remote Similarity	NPD6933	Approved
0.6087	Remote Similarity	NPD4202	Approved
0.6083	Remote Similarity	NPD5225	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