NPASS Compound

Structure

NPC174991 OpenBabel07101719522D 30 31 0 0 0 0 0 0 0 0999 V2000 -6.0622 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 -0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.1244 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 19 1 0 0 0 0 2 20 1 0 0 0 0 3 21 1 0 0 0 0 4 27 1 0 0 0 0 5 27 1 0 0 0 0 6 8 1 0 0 0 0 6 9 1 0 0 0 0 7 10 1 0 0 0 0 7 17 1 0 0 0 0 8 19 1 0 0 0 0 9 20 2 0 0 0 0 10 21 1 0 0 0 0 11 13 1 0 0 0 0 11 19 2 0 0 0 0 12 15 1 0 0 0 0 12 20 1 0 0 0 0 13 22 1 0 0 0 0 14 16 1 0 0 0 0 14 23 2 0 0 0 0 15 24 1 0 0 0 0 16 25 2 0 0 0 0 17 27 1 0 0 0 0 18 22 2 0 0 0 0 18 23 1 0 0 0 0 21 24 2 0 0 0 0 22 25 1 0 0 0 0 23 26 1 0 0 0 0 24 27 1 0 0 0 0 25 28 1 0 0 0 0 26 29 1 0 0 0 0 26 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	410.28
Volume:	466.351
LogP:	7.171
LogD:	5.394
LogS:	-3.237
# Rotatable Bonds:	9
TPSA:	57.53
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.412
Synthetic Accessibility Score:	2.998
Fsp3:	0.519
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-5.124
MDCK Permeability:	2.1025405658292584e-05
Pgp-inhibitor:	0.204
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.021
20% Bioavailability (F20%):	0.077
30% Bioavailability (F30%):	0.034

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022
Plasma Protein Binding (PPB):	96.66386413574219%
Volume Distribution (VD):	0.427
Pgp-substrate:	0.38523587584495544%

ADMET: Metabolism

CYP1A2-inhibitor:	0.191
CYP1A2-substrate:	0.339
CYP2C19-inhibitor:	0.221
CYP2C19-substrate:	0.064
CYP2C9-inhibitor:	0.332
CYP2C9-substrate:	0.872
CYP2D6-inhibitor:	0.731
CYP2D6-substrate:	0.317
CYP3A4-inhibitor:	0.085
CYP3A4-substrate:	0.069

ADMET: Excretion

Clearance (CL):	2.451
Half-life (T1/2):	0.465

ADMET: Toxicity

hERG Blockers:	0.012
Human Hepatotoxicity (H-HT):	0.712
Drug-inuced Liver Injury (DILI):	0.036
AMES Toxicity:	0.002
Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.142
Skin Sensitization:	0.666
Carcinogencity:	0.014
Eye Corrosion:	0.006
Eye Irritation:	0.614
Respiratory Toxicity:	0.063

Download Data

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

Natural Product: NPC174991

Natural Product ID:	NPC174991
*Common Name:**	Cacospongin D
IUPAC Name:	3-[(2E,6E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,6-dienyl]-4-hydroxybenzoic acid
Synonyms:	Cacospongin D
Standard InCHIKey:	QQJLPYXRXOCODZ-ZQYJZOSASA-N
Standard InCHI:	InChI=1S/C27H38O3/c1-19(11-13-22-18-23(26(29)30)14-16-25(22)28)8-6-9-20(2)12-15-24-21(3)10-7-17-27(24,4)5/h9,11,14,16,18,28H,6-8,10,12-13,15,17H2,1-5H3,(H,29,30)/b19-11+,20-9+
SMILES:	C/C(=CCc1cc(ccc1O)C(=O)O)/CC/C=C(C)/CCC1=C(C)CCCC1(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL224100
PubChem CID:	10251028
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] 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
NPO32440	Cacospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11720537]
NPO32440	Cacospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17346077]

☑ 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
MIC	3

Activity Type	# Activity
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	=	20.0	ug.mL-1	PMID[569766]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	400.0	ug.mL-1	PMID[569766]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	400.0	ug.mL-1	PMID[569766]

☑ 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 NPC174991 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	268
0.1-0.2	1396
0.2-0.3	3126
0.3-0.4	8133
0.4-0.5	11336
0.5-0.6	6271
0.6-0.7	9184
0.7-0.8	2751
0.8-0.85	199
0.85-0.9	23
0.9-0.95	5
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
0.9587	High Similarity	NPC193203
0.9508	High Similarity	NPC117899
0.9483	High Similarity	NPC273282
0.9483	High Similarity	NPC161943
0.9483	High Similarity	NPC474890
0.9426	High Similarity	NPC229894
0.9355	High Similarity	NPC18798
0.931	High Similarity	NPC83718
0.8984	High Similarity	NPC477594
0.8934	High Similarity	NPC67300
0.8915	High Similarity	NPC477596
0.8889	High Similarity	NPC242136
0.88	High Similarity	NPC473751
0.879	High Similarity	NPC184219
0.878	High Similarity	NPC475192
0.8779	High Similarity	NPC477592
0.8712	High Similarity	NPC477593
0.8651	High Similarity	NPC254492
0.8651	High Similarity	NPC204579
0.8595	High Similarity	NPC174087
0.8583	High Similarity	NPC72667
0.8547	High Similarity	NPC95172
0.8538	High Similarity	NPC302844
0.8534	High Similarity	NPC29883
0.8519	High Similarity	NPC477595
0.8516	High Similarity	NPC473744
0.8504	High Similarity	NPC110211
0.8504	High Similarity	NPC62952
0.848	Intermediate Similarity	NPC282577
0.848	Intermediate Similarity	NPC309765
0.8462	Intermediate Similarity	NPC470039
0.8455	Intermediate Similarity	NPC473767
0.845	Intermediate Similarity	NPC171460
0.8448	Intermediate Similarity	NPC184658
0.8438	Intermediate Similarity	NPC176130
0.8438	Intermediate Similarity	NPC78364
0.8438	Intermediate Similarity	NPC162612
0.8438	Intermediate Similarity	NPC116513
0.8438	Intermediate Similarity	NPC121104
0.8438	Intermediate Similarity	NPC23126
0.8438	Intermediate Similarity	NPC72158
0.8438	Intermediate Similarity	NPC84672
0.8438	Intermediate Similarity	NPC266689
0.8438	Intermediate Similarity	NPC69424
0.8438	Intermediate Similarity	NPC169250
0.8438	Intermediate Similarity	NPC105157
0.8438	Intermediate Similarity	NPC103356
0.8438	Intermediate Similarity	NPC100067
0.8438	Intermediate Similarity	NPC30501
0.8438	Intermediate Similarity	NPC98254
0.8438	Intermediate Similarity	NPC190043
0.8406	Intermediate Similarity	NPC97188
0.84	Intermediate Similarity	NPC303737
0.8394	Intermediate Similarity	NPC271451
0.8385	Intermediate Similarity	NPC327457
0.8385	Intermediate Similarity	NPC17840
0.8385	Intermediate Similarity	NPC86774
0.8385	Intermediate Similarity	NPC247477
0.8376	Intermediate Similarity	NPC226699
0.8372	Intermediate Similarity	NPC21305
0.8372	Intermediate Similarity	NPC473017
0.8372	Intermediate Similarity	NPC3009
0.8372	Intermediate Similarity	NPC96024
0.8372	Intermediate Similarity	NPC221777
0.8362	Intermediate Similarity	NPC243677
0.8362	Intermediate Similarity	NPC303141
0.8361	Intermediate Similarity	NPC131192
0.8359	Intermediate Similarity	NPC267846
0.8359	Intermediate Similarity	NPC328983
0.8346	Intermediate Similarity	NPC290803
0.8346	Intermediate Similarity	NPC199273
0.8345	Intermediate Similarity	NPC469498
0.8333	Intermediate Similarity	NPC91105
0.8333	Intermediate Similarity	NPC180261
0.8333	Intermediate Similarity	NPC37299
0.8321	Intermediate Similarity	NPC473777
0.832	Intermediate Similarity	NPC164852
0.832	Intermediate Similarity	NPC241001
0.832	Intermediate Similarity	NPC216216
0.8319	Intermediate Similarity	NPC222905
0.8319	Intermediate Similarity	NPC116842
0.8308	Intermediate Similarity	NPC194979
0.8308	Intermediate Similarity	NPC276238
0.8308	Intermediate Similarity	NPC474998
0.8295	Intermediate Similarity	NPC316625
0.8295	Intermediate Similarity	NPC209959
0.8295	Intermediate Similarity	NPC329205
0.8291	Intermediate Similarity	NPC6984
0.8284	Intermediate Similarity	NPC118919
0.8281	Intermediate Similarity	NPC123506
0.8279	Intermediate Similarity	NPC322197
0.8273	Intermediate Similarity	NPC258856
0.8271	Intermediate Similarity	NPC204582
0.8271	Intermediate Similarity	NPC475088
0.8268	Intermediate Similarity	NPC472029
0.8268	Intermediate Similarity	NPC65761
0.8268	Intermediate Similarity	NPC275145
0.8264	Intermediate Similarity	NPC211421
0.8254	Intermediate Similarity	NPC215392
0.8254	Intermediate Similarity	NPC295034
0.8244	Intermediate Similarity	NPC108129
0.8244	Intermediate Similarity	NPC109778
0.824	Intermediate Similarity	NPC159525
0.8231	Intermediate Similarity	NPC2401
0.8226	Intermediate Similarity	NPC27633
0.8226	Intermediate Similarity	NPC94298
0.8222	Intermediate Similarity	NPC53001
0.8217	Intermediate Similarity	NPC15837
0.819	Intermediate Similarity	NPC470202
0.8189	Intermediate Similarity	NPC121168
0.8182	Intermediate Similarity	NPC475042
0.8182	Intermediate Similarity	NPC471851
0.8175	Intermediate Similarity	NPC301987
0.8175	Intermediate Similarity	NPC244994
0.8175	Intermediate Similarity	NPC149246
0.8175	Intermediate Similarity	NPC179092
0.8175	Intermediate Similarity	NPC190971
0.8175	Intermediate Similarity	NPC292665
0.8175	Intermediate Similarity	NPC35856
0.8175	Intermediate Similarity	NPC178395
0.8175	Intermediate Similarity	NPC26433
0.8175	Intermediate Similarity	NPC222876
0.8175	Intermediate Similarity	NPC115188
0.8175	Intermediate Similarity	NPC159760
0.8175	Intermediate Similarity	NPC272454
0.8168	Intermediate Similarity	NPC303910
0.8162	Intermediate Similarity	NPC87723
0.816	Intermediate Similarity	NPC161617
0.816	Intermediate Similarity	NPC158222
0.8151	Intermediate Similarity	NPC17525
0.8145	Intermediate Similarity	NPC160199
0.8143	Intermediate Similarity	NPC75295
0.814	Intermediate Similarity	NPC137416
0.814	Intermediate Similarity	NPC49938
0.814	Intermediate Similarity	NPC475733
0.8134	Intermediate Similarity	NPC166480
0.8134	Intermediate Similarity	NPC282780
0.812	Intermediate Similarity	NPC175738
0.8112	Intermediate Similarity	NPC37642
0.811	Intermediate Similarity	NPC154696
0.811	Intermediate Similarity	NPC156139
0.811	Intermediate Similarity	NPC162935
0.811	Intermediate Similarity	NPC249340
0.8106	Intermediate Similarity	NPC259942
0.8102	Intermediate Similarity	NPC19622
0.8102	Intermediate Similarity	NPC112789
0.8099	Intermediate Similarity	NPC17600
0.8092	Intermediate Similarity	NPC2596
0.8088	Intermediate Similarity	NPC194579
0.8083	Intermediate Similarity	NPC471954
0.8083	Intermediate Similarity	NPC75272
0.808	Intermediate Similarity	NPC241089
0.808	Intermediate Similarity	NPC249435
0.808	Intermediate Similarity	NPC184527
0.8077	Intermediate Similarity	NPC473691
0.8074	Intermediate Similarity	NPC249272
0.8074	Intermediate Similarity	NPC470210
0.8067	Intermediate Similarity	NPC228737
0.8067	Intermediate Similarity	NPC141523
0.8062	Intermediate Similarity	NPC474803
0.806	Intermediate Similarity	NPC49742
0.806	Intermediate Similarity	NPC213485
0.806	Intermediate Similarity	NPC40524
0.806	Intermediate Similarity	NPC138472
0.806	Intermediate Similarity	NPC78307
0.806	Intermediate Similarity	NPC139074
0.806	Intermediate Similarity	NPC477139
0.806	Intermediate Similarity	NPC239855
0.8049	Intermediate Similarity	NPC114918
0.8047	Intermediate Similarity	NPC133909
0.8047	Intermediate Similarity	NPC32032
0.8047	Intermediate Similarity	NPC139171
0.8047	Intermediate Similarity	NPC297193
0.8047	Intermediate Similarity	NPC244351
0.8047	Intermediate Similarity	NPC68167
0.8047	Intermediate Similarity	NPC66252
0.8043	Intermediate Similarity	NPC172311
0.8043	Intermediate Similarity	NPC275903
0.8043	Intermediate Similarity	NPC469911
0.8042	Intermediate Similarity	NPC52931
0.8033	Intermediate Similarity	NPC231717
0.8031	Intermediate Similarity	NPC259703
0.8031	Intermediate Similarity	NPC32322
0.8031	Intermediate Similarity	NPC297186
0.803	Intermediate Similarity	NPC476119
0.803	Intermediate Similarity	NPC92624
0.8029	Intermediate Similarity	NPC23870
0.8029	Intermediate Similarity	NPC230811
0.8029	Intermediate Similarity	NPC473622
0.8028	Intermediate Similarity	NPC477483
0.8028	Intermediate Similarity	NPC325032
0.8017	Intermediate Similarity	NPC52472
0.8016	Intermediate Similarity	NPC233165
0.8016	Intermediate Similarity	NPC42657
0.8016	Intermediate Similarity	NPC61779
0.8016	Intermediate Similarity	NPC184579
0.8015	Intermediate Similarity	NPC291454
0.8015	Intermediate Similarity	NPC37512
0.8014	Intermediate Similarity	NPC208293
0.8	Intermediate Similarity	NPC121259

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 NPC174991 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	278
0.1-0.2	916
0.2-0.3	1400
0.3-0.4	2526
0.4-0.5	2278
0.5-0.6	1216
0.6-0.7	446
0.7-0.8	86
0.8-0.85	2
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8607	High Similarity	NPD4196	Clinical (unspecified phase)
0.8534	High Similarity	NPD9265	Clinical (unspecified phase)
0.8462	Intermediate Similarity	NPD6831	Clinical (unspecified phase)
0.8226	Intermediate Similarity	NPD9545	Approved
0.8	Intermediate Similarity	NPD1164	Approved
0.7914	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7851	Intermediate Similarity	NPD9266	Approved
0.7851	Intermediate Similarity	NPD74	Approved
0.7826	Intermediate Similarity	NPD5408	Approved
0.7826	Intermediate Similarity	NPD5404	Approved
0.7826	Intermediate Similarity	NPD5405	Approved
0.7826	Intermediate Similarity	NPD5406	Approved
0.7778	Intermediate Similarity	NPD9493	Approved
0.7769	Intermediate Similarity	NPD9267	Approved
0.7769	Intermediate Similarity	NPD9264	Approved
0.7769	Intermediate Similarity	NPD9263	Approved
0.776	Intermediate Similarity	NPD5951	Approved
0.773	Intermediate Similarity	NPD7003	Approved
0.7704	Intermediate Similarity	NPD3764	Approved
0.7698	Intermediate Similarity	NPD2935	Discontinued
0.7692	Intermediate Similarity	NPD1201	Approved
0.7674	Intermediate Similarity	NPD2932	Approved
0.7638	Intermediate Similarity	NPD405	Clinical (unspecified phase)
0.7626	Intermediate Similarity	NPD1509	Clinical (unspecified phase)
0.7606	Intermediate Similarity	NPD4628	Phase 3
0.7594	Intermediate Similarity	NPD1470	Approved
0.7591	Intermediate Similarity	NPD1240	Approved
0.7551	Intermediate Similarity	NPD7458	Discontinued
0.7538	Intermediate Similarity	NPD3019	Approved
0.7538	Intermediate Similarity	NPD7163	Clinical (unspecified phase)
0.7521	Intermediate Similarity	NPD1809	Phase 2
0.75	Intermediate Similarity	NPD3972	Approved
0.75	Intermediate Similarity	NPD2799	Discontinued
0.7483	Intermediate Similarity	NPD3750	Approved
0.7482	Intermediate Similarity	NPD1607	Approved
0.7482	Intermediate Similarity	NPD6651	Approved
0.7464	Intermediate Similarity	NPD943	Approved
0.7438	Intermediate Similarity	NPD9261	Approved
0.7391	Intermediate Similarity	NPD6663	Approved
0.7373	Intermediate Similarity	NPD2859	Approved
0.7373	Intermediate Similarity	NPD2860	Approved
0.7368	Intermediate Similarity	NPD9269	Phase 2
0.7361	Intermediate Similarity	NPD8166	Discontinued
0.7361	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7355	Intermediate Similarity	NPD846	Approved
0.7355	Intermediate Similarity	NPD940	Approved
0.7353	Intermediate Similarity	NPD5736	Approved
0.7351	Intermediate Similarity	NPD7819	Suspended
0.7344	Intermediate Similarity	NPD9281	Approved
0.7343	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD7411	Suspended
0.7329	Intermediate Similarity	NPD7390	Discontinued
0.7328	Intermediate Similarity	NPD9268	Approved
0.732	Intermediate Similarity	NPD7075	Discontinued
0.7319	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7295	Intermediate Similarity	NPD1929	Approved
0.7295	Intermediate Similarity	NPD1931	Clinical (unspecified phase)
0.7295	Intermediate Similarity	NPD1930	Approved
0.7288	Intermediate Similarity	NPD2934	Approved
0.7288	Intermediate Similarity	NPD2933	Approved
0.7288	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.7287	Intermediate Similarity	NPD255	Approved
0.7287	Intermediate Similarity	NPD256	Approved
0.7279	Intermediate Similarity	NPD7410	Clinical (unspecified phase)
0.7279	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD4626	Approved
0.7254	Intermediate Similarity	NPD1510	Phase 2
0.7241	Intermediate Similarity	NPD9258	Approved
0.7241	Intermediate Similarity	NPD9256	Approved
0.7239	Intermediate Similarity	NPD9717	Approved
0.7237	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7206	Intermediate Similarity	NPD2797	Approved
0.7206	Intermediate Similarity	NPD1203	Approved
0.7203	Intermediate Similarity	NPD845	Approved
0.7194	Intermediate Similarity	NPD2313	Discontinued
0.719	Intermediate Similarity	NPD3020	Approved
0.7172	Intermediate Similarity	NPD2800	Approved
0.7163	Intermediate Similarity	NPD230	Phase 1
0.7162	Intermediate Similarity	NPD2532	Approved
0.7162	Intermediate Similarity	NPD2534	Approved
0.7162	Intermediate Similarity	NPD2533	Approved
0.7153	Intermediate Similarity	NPD2344	Approved
0.7153	Intermediate Similarity	NPD2798	Approved
0.7152	Intermediate Similarity	NPD6599	Discontinued
0.7143	Intermediate Similarity	NPD7768	Phase 2
0.7133	Intermediate Similarity	NPD3748	Approved
0.7133	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7132	Intermediate Similarity	NPD1283	Approved
0.7111	Intermediate Similarity	NPD1608	Approved
0.7109	Intermediate Similarity	NPD6124	Clinical (unspecified phase)
0.7103	Intermediate Similarity	NPD1549	Phase 2
0.7101	Intermediate Similarity	NPD4208	Discontinued
0.7095	Intermediate Similarity	NPD6799	Approved
0.7086	Intermediate Similarity	NPD3226	Approved
0.7078	Intermediate Similarity	NPD8438	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD3268	Approved
0.7059	Intermediate Similarity	NPD6801	Discontinued
0.7059	Intermediate Similarity	NPD1755	Approved
0.7055	Intermediate Similarity	NPD1243	Approved
0.705	Intermediate Similarity	NPD6832	Phase 2
0.7049	Intermediate Similarity	NPD2066	Phase 3
0.7039	Intermediate Similarity	NPD4380	Phase 2
0.7037	Intermediate Similarity	NPD422	Phase 1
0.7034	Intermediate Similarity	NPD2346	Discontinued
0.7034	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7029	Intermediate Similarity	NPD6007	Clinical (unspecified phase)
0.7025	Intermediate Similarity	NPD6232	Discontinued
0.7014	Intermediate Similarity	NPD4308	Phase 3
0.7007	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6273	Approved
0.7	Intermediate Similarity	NPD7008	Discontinued
0.7	Intermediate Similarity	NPD7473	Discontinued
0.7	Intermediate Similarity	NPD7159	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD1241	Discontinued
0.6992	Remote Similarity	NPD1759	Phase 1
0.6992	Remote Similarity	NPD289	Clinical (unspecified phase)
0.697	Remote Similarity	NPD9568	Approved
0.6968	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD2796	Approved
0.6966	Remote Similarity	NPD6100	Approved
0.6966	Remote Similarity	NPD4477	Approved
0.6966	Remote Similarity	NPD6099	Approved
0.6966	Remote Similarity	NPD4476	Approved
0.6963	Remote Similarity	NPD3023	Approved
0.6963	Remote Similarity	NPD3026	Approved
0.696	Remote Similarity	NPD1237	Approved
0.6959	Remote Similarity	NPD2309	Approved
0.6953	Remote Similarity	NPD4750	Phase 3
0.6947	Remote Similarity	NPD2629	Approved
0.6942	Remote Similarity	NPD844	Approved
0.694	Remote Similarity	NPD5691	Approved
0.694	Remote Similarity	NPD3025	Approved
0.694	Remote Similarity	NPD3024	Approved
0.6937	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD7422	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD4207	Discontinued
0.6923	Remote Similarity	NPD7635	Approved
0.6918	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6917	Remote Similarity	NPD5122	Clinical (unspecified phase)
0.6917	Remote Similarity	NPD1202	Approved
0.6917	Remote Similarity	NPD1758	Phase 1
0.6913	Remote Similarity	NPD3300	Phase 2
0.6912	Remote Similarity	NPD1281	Approved
0.6903	Remote Similarity	NPD2393	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD520	Approved
0.6899	Remote Similarity	NPD2181	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD9259	Approved
0.6897	Remote Similarity	NPD9257	Approved
0.6892	Remote Similarity	NPD3400	Discontinued
0.6889	Remote Similarity	NPD17	Approved
0.6889	Remote Similarity	NPD1778	Approved
0.6887	Remote Similarity	NPD5049	Phase 3
0.6884	Remote Similarity	NPD1876	Approved
0.6879	Remote Similarity	NPD3749	Approved
0.6867	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.6861	Remote Similarity	NPD1481	Phase 2
0.6857	Remote Similarity	NPD9494	Approved
0.6849	Remote Similarity	NPD1551	Phase 2
0.6846	Remote Similarity	NPD2354	Approved
0.6846	Remote Similarity	NPD1609	Clinical (unspecified phase)
0.6838	Remote Similarity	NPD3847	Discontinued
0.6833	Remote Similarity	NPD1088	Approved
0.6831	Remote Similarity	NPD6798	Discontinued
0.6815	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.681	Remote Similarity	NPD5844	Phase 1
0.681	Remote Similarity	NPD111	Approved
0.681	Remote Similarity	NPD7286	Phase 2
0.6806	Remote Similarity	NPD6355	Discontinued
0.68	Remote Similarity	NPD7236	Approved
0.68	Remote Similarity	NPD643	Clinical (unspecified phase)
0.6794	Remote Similarity	NPD5277	Phase 2
0.6788	Remote Similarity	NPD1535	Discovery
0.6783	Remote Similarity	NPD8032	Phase 2
0.6781	Remote Similarity	NPD3299	Clinical (unspecified phase)
0.6781	Remote Similarity	NPD7033	Discontinued
0.6765	Remote Similarity	NPD3412	Clinical (unspecified phase)
0.6765	Remote Similarity	NPD4589	Approved
0.6763	Remote Similarity	NPD3225	Approved
0.6753	Remote Similarity	NPD5808	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD288	Approved
0.6744	Remote Similarity	NPD2182	Approved
0.6741	Remote Similarity	NPD1894	Discontinued
0.6741	Remote Similarity	NPD3091	Approved
0.6739	Remote Similarity	NPD4878	Approved
0.6738	Remote Similarity	NPD4212	Discontinued
0.6736	Remote Similarity	NPD4307	Phase 2
0.6736	Remote Similarity	NPD4060	Phase 1
0.6733	Remote Similarity	NPD6190	Approved
0.6732	Remote Similarity	NPD920	Approved
0.6727	Remote Similarity	NPD5953	Discontinued
0.6723	Remote Similarity	NPD800	Approved
0.6721	Remote Similarity	NPD688	Clinical (unspecified phase)
0.6719	Remote Similarity	NPD3134	Approved
0.6714	Remote Similarity	NPD3266	Approved
0.6714	Remote Similarity	NPD3267	Approved
0.6713	Remote Similarity	NPD411	Approved
0.6711	Remote Similarity	NPD642	Clinical (unspecified phase)
0.6711	Remote Similarity	NPD7004	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