NPASS Compound

Structure

NPC475481 OpenBabel07101718232D 24 25 0 0 1 0 0 0 0 0999 V2000 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1213 -3.1213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5708 0.7424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0544 -2.3741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4142 -2.4142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6049 0.4836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1305 -1.9914 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 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9659 -0.7412 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6730 -1.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3461 -0.4824 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 1 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 2.6390 -1.1895 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3301 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6049 -1.4483 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 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 6 1 0 0 0 0 2 7 1 0 0 0 0 3 8 1 0 0 0 0 4 9 1 0 0 0 0 5 21 1 0 0 0 0 7 14 1 0 0 0 0 10 17 1 0 0 0 0 11 13 1 0 0 0 0 11 19 1 0 0 0 0 12 14 2 0 0 0 0 12 19 1 0 0 0 0 13 6 1 6 0 0 0 13 16 1 0 0 0 0 15 8 1 1 0 0 0 15 18 1 0 0 0 0 15 22 1 0 0 0 0 16 10 1 6 0 0 0 16 23 1 0 0 0 0 17 20 2 0 0 0 0 17 21 1 0 0 0 0 18 14 1 1 0 0 0 18 22 1 0 0 0 0 19 9 1 6 0 0 0 19 24 1 0 0 0 0 23 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	340.22
Volume:	358.745
LogP:	4.022
LogD:	3.867
LogS:	-4.74
# Rotatable Bonds:	9
TPSA:	57.29
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.29
Synthetic Accessibility Score:	4.908
Fsp3:	0.842
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.626
MDCK Permeability:	2.2259582692640834e-05
Pgp-inhibitor:	0.993
Pgp-substrate:	0.009
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.055

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.13
Plasma Protein Binding (PPB):	87.3218994140625%
Volume Distribution (VD):	1.148
Pgp-substrate:	3.130720853805542%

ADMET: Metabolism

CYP1A2-inhibitor:	0.038
CYP1A2-substrate:	0.684
CYP2C19-inhibitor:	0.303
CYP2C19-substrate:	0.9
CYP2C9-inhibitor:	0.544
CYP2C9-substrate:	0.049
CYP2D6-inhibitor:	0.043
CYP2D6-substrate:	0.208
CYP3A4-inhibitor:	0.904
CYP3A4-substrate:	0.77

ADMET: Excretion

Clearance (CL):	7.968
Half-life (T1/2):	0.393

ADMET: Toxicity

hERG Blockers:	0.055
Human Hepatotoxicity (H-HT):	0.596
Drug-inuced Liver Injury (DILI):	0.767
AMES Toxicity:	0.239
Rat Oral Acute Toxicity:	0.12
Maximum Recommended Daily Dose:	0.905
Skin Sensitization:	0.7
Carcinogencity:	0.733
Eye Corrosion:	0.015
Eye Irritation:	0.07
Respiratory Toxicity:	0.965

Download Data

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

Natural Product: NPC475481

Natural Product ID:	NPC475481
*Common Name:**	Plakorstatin 2
IUPAC Name:	methyl 2-[(3S,4S,6R)-4,6-diethyl-6-[(E)-2-[(2S,3R)-3-ethyloxiran-2-yl]but-1-enyl]dioxan-3-yl]acetate
Synonyms:	Plakorstatin 2
Standard InCHIKey:	CFXNHQNIKKFEDQ-SIQOOVPDSA-N
Standard InCHI:	InChI=1S/C19H32O5/c1-6-13-11-19(9-4,24-23-16(13)10-17(20)21-5)12-14(7-2)18-15(8-3)22-18/h12-13,15-16,18H,6-11H2,1-5H3/b14-12+/t13-,15+,16-,18-,19+/m0/s1
SMILES:	CC[C@H]1C[C@@](CC)(OO[C@H]1CC(=O)OC)/C=C(/[C@@H]1O[C@@H]1CC)CC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL506384
PubChem CID:	44585488
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000368] Dioxanes [CHEMONTID:0001312] 1,2-dioxanes

*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
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	Palauan	n.a.	PMID[12350142]
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	Indo-Pacific	n.a.	PMID[15387674]
NPO2117	Plakortis nigra	Species	Plakinidae	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	2
GI50	6

Activity Type	# Activity
Cell Line	8

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1081	Cell Line	BXPC-3	Homo sapiens	GI50	=	6.4	n.a.	PMID[514735]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	3.8	n.a.	PMID[514735]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	=	1.6	n.a.	PMID[514735]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	>	10.0	n.a.	PMID[514735]
NPT575	Cell Line	KM-20L2	Homo sapiens	GI50	=	6.7	n.a.	PMID[514735]
NPT90	Cell Line	DU-145	Homo sapiens	GI50	=	1.7	n.a.	PMID[514735]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.91	ug ml-1	PMID[514735]
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.91	ug ml-1	PMID[514736]

☑ 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 NPC475481 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	201
0.1-0.2	1276
0.2-0.3	5357
0.3-0.4	13621
0.4-0.5	11505
0.5-0.6	7139
0.6-0.7	3166
0.7-0.8	402
0.8-0.85	24
0.85-0.9	4
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC79277
0.9079	High Similarity	NPC474447
0.8816	High Similarity	NPC474551
0.8765	High Similarity	NPC475989
0.8684	High Similarity	NPC472018
0.8684	High Similarity	NPC167145
0.8684	High Similarity	NPC474543
0.8684	High Similarity	NPC238425
0.8608	High Similarity	NPC474341
0.8608	High Similarity	NPC121200
0.8571	High Similarity	NPC330016
0.8519	High Similarity	NPC141810
0.8481	Intermediate Similarity	NPC281296
0.8481	Intermediate Similarity	NPC476264
0.8481	Intermediate Similarity	NPC476325
0.8462	Intermediate Similarity	NPC60718
0.8421	Intermediate Similarity	NPC69462
0.8415	Intermediate Similarity	NPC475936
0.8354	Intermediate Similarity	NPC239127
0.8313	Intermediate Similarity	NPC53867
0.8289	Intermediate Similarity	NPC107130
0.8276	Intermediate Similarity	NPC51653
0.8272	Intermediate Similarity	NPC617
0.8228	Intermediate Similarity	NPC199445
0.8228	Intermediate Similarity	NPC255060
0.8182	Intermediate Similarity	NPC475310
0.8182	Intermediate Similarity	NPC472017
0.8125	Intermediate Similarity	NPC469514
0.8125	Intermediate Similarity	NPC301525
0.8095	Intermediate Similarity	NPC69469
0.8095	Intermediate Similarity	NPC475842
0.8077	Intermediate Similarity	NPC477084
0.8072	Intermediate Similarity	NPC476988
0.8049	Intermediate Similarity	NPC82488
0.8049	Intermediate Similarity	NPC308545
0.8046	Intermediate Similarity	NPC475902
0.8025	Intermediate Similarity	NPC97516
0.8025	Intermediate Similarity	NPC474760
0.8023	Intermediate Similarity	NPC50637
0.8023	Intermediate Similarity	NPC476982
0.8	Intermediate Similarity	NPC475861
0.7976	Intermediate Similarity	NPC35556
0.7975	Intermediate Similarity	NPC135703
0.7955	Intermediate Similarity	NPC475971
0.7955	Intermediate Similarity	NPC471342
0.7955	Intermediate Similarity	NPC469866
0.7952	Intermediate Similarity	NPC469920
0.7931	Intermediate Similarity	NPC266957
0.7907	Intermediate Similarity	NPC474369
0.7901	Intermediate Similarity	NPC59602
0.7901	Intermediate Similarity	NPC152754
0.7901	Intermediate Similarity	NPC271070
0.7901	Intermediate Similarity	NPC476987
0.7901	Intermediate Similarity	NPC266119
0.7882	Intermediate Similarity	NPC475947
0.7882	Intermediate Similarity	NPC170377
0.7882	Intermediate Similarity	NPC170286
0.7875	Intermediate Similarity	NPC140287
0.7865	Intermediate Similarity	NPC475748
0.7857	Intermediate Similarity	NPC172309
0.7857	Intermediate Similarity	NPC117960
0.7857	Intermediate Similarity	NPC14044
0.7857	Intermediate Similarity	NPC471325
0.7857	Intermediate Similarity	NPC25684
0.7857	Intermediate Similarity	NPC301477
0.7857	Intermediate Similarity	NPC281949
0.7831	Intermediate Similarity	NPC471740
0.7821	Intermediate Similarity	NPC269841
0.7816	Intermediate Similarity	NPC469483
0.7816	Intermediate Similarity	NPC476104
0.7805	Intermediate Similarity	NPC476028
0.7805	Intermediate Similarity	NPC141789
0.7805	Intermediate Similarity	NPC171204
0.7802	Intermediate Similarity	NPC471147
0.7802	Intermediate Similarity	NPC140543
0.7791	Intermediate Similarity	NPC471343
0.7791	Intermediate Similarity	NPC72464
0.7778	Intermediate Similarity	NPC20713
0.7765	Intermediate Similarity	NPC85772
0.7753	Intermediate Similarity	NPC115179
0.7753	Intermediate Similarity	NPC166919
0.7753	Intermediate Similarity	NPC106040
0.7738	Intermediate Similarity	NPC474739
0.7727	Intermediate Similarity	NPC86005
0.7727	Intermediate Similarity	NPC231889
0.7727	Intermediate Similarity	NPC471739
0.7727	Intermediate Similarity	NPC474765
0.7727	Intermediate Similarity	NPC471738
0.7717	Intermediate Similarity	NPC475659
0.7711	Intermediate Similarity	NPC127526
0.7701	Intermediate Similarity	NPC471344
0.7701	Intermediate Similarity	NPC474547
0.7683	Intermediate Similarity	NPC475744
0.7683	Intermediate Similarity	NPC474316
0.7683	Intermediate Similarity	NPC476985
0.7674	Intermediate Similarity	NPC474703
0.7674	Intermediate Similarity	NPC272814
0.7674	Intermediate Similarity	NPC476983
0.7674	Intermediate Similarity	NPC318468
0.7654	Intermediate Similarity	NPC476355
0.7654	Intermediate Similarity	NPC474758
0.7647	Intermediate Similarity	NPC474894
0.7647	Intermediate Similarity	NPC286229
0.7634	Intermediate Similarity	NPC230800
0.7634	Intermediate Similarity	NPC473859
0.7625	Intermediate Similarity	NPC126061
0.7625	Intermediate Similarity	NPC163003
0.7619	Intermediate Similarity	NPC268502
0.7619	Intermediate Similarity	NPC254996
0.7619	Intermediate Similarity	NPC178277
0.7619	Intermediate Similarity	NPC19841
0.7619	Intermediate Similarity	NPC471537
0.7619	Intermediate Similarity	NPC471299
0.7619	Intermediate Similarity	NPC270126
0.7619	Intermediate Similarity	NPC113363
0.7614	Intermediate Similarity	NPC261253
0.7614	Intermediate Similarity	NPC474045
0.7614	Intermediate Similarity	NPC116575
0.7609	Intermediate Similarity	NPC476267
0.7595	Intermediate Similarity	NPC477448
0.7595	Intermediate Similarity	NPC101622
0.7595	Intermediate Similarity	NPC477449
0.759	Intermediate Similarity	NPC470240
0.759	Intermediate Similarity	NPC84360
0.759	Intermediate Similarity	NPC107668
0.759	Intermediate Similarity	NPC476794
0.759	Intermediate Similarity	NPC41780
0.759	Intermediate Similarity	NPC122847
0.759	Intermediate Similarity	NPC187568
0.7586	Intermediate Similarity	NPC70424
0.7586	Intermediate Similarity	NPC474776
0.7586	Intermediate Similarity	NPC158756
0.7586	Intermediate Similarity	NPC243618
0.7586	Intermediate Similarity	NPC9868
0.7586	Intermediate Similarity	NPC159635
0.7579	Intermediate Similarity	NPC469551
0.7558	Intermediate Similarity	NPC89555
0.7558	Intermediate Similarity	NPC474252
0.7558	Intermediate Similarity	NPC475690
0.7556	Intermediate Similarity	NPC151770
0.7556	Intermediate Similarity	NPC83423
0.7553	Intermediate Similarity	NPC471140
0.7529	Intermediate Similarity	NPC233377
0.7529	Intermediate Similarity	NPC474510
0.7529	Intermediate Similarity	NPC281132
0.7528	Intermediate Similarity	NPC72513
0.7528	Intermediate Similarity	NPC475703
0.7526	Intermediate Similarity	NPC19239
0.7526	Intermediate Similarity	NPC474166
0.75	Intermediate Similarity	NPC261380
0.75	Intermediate Similarity	NPC470755
0.75	Intermediate Similarity	NPC228451
0.75	Intermediate Similarity	NPC469660
0.75	Intermediate Similarity	NPC474005
0.75	Intermediate Similarity	NPC165383
0.75	Intermediate Similarity	NPC475838
0.75	Intermediate Similarity	NPC78089
0.75	Intermediate Similarity	NPC128276
0.75	Intermediate Similarity	NPC4299
0.75	Intermediate Similarity	NPC125674
0.75	Intermediate Similarity	NPC255307
0.7473	Intermediate Similarity	NPC316228
0.7471	Intermediate Similarity	NPC16488
0.7471	Intermediate Similarity	NPC222358
0.7471	Intermediate Similarity	NPC108045
0.7471	Intermediate Similarity	NPC475622
0.747	Intermediate Similarity	NPC235906
0.747	Intermediate Similarity	NPC123360
0.7468	Intermediate Similarity	NPC276290
0.7447	Intermediate Similarity	NPC476315
0.7447	Intermediate Similarity	NPC473291
0.7444	Intermediate Similarity	NPC476805
0.7444	Intermediate Similarity	NPC476803
0.7444	Intermediate Similarity	NPC469631
0.7444	Intermediate Similarity	NPC469628
0.7444	Intermediate Similarity	NPC469653
0.7444	Intermediate Similarity	NPC471047
0.7444	Intermediate Similarity	NPC475906
0.7442	Intermediate Similarity	NPC52861
0.7436	Intermediate Similarity	NPC284447
0.7419	Intermediate Similarity	NPC473330
0.7419	Intermediate Similarity	NPC474247
0.7419	Intermediate Similarity	NPC473316
0.7416	Intermediate Similarity	NPC279859
0.7416	Intermediate Similarity	NPC315395
0.7416	Intermediate Similarity	NPC305475
0.7416	Intermediate Similarity	NPC204048
0.7416	Intermediate Similarity	NPC261721
0.7416	Intermediate Similarity	NPC198314
0.7416	Intermediate Similarity	NPC38576
0.7416	Intermediate Similarity	NPC475461
0.7416	Intermediate Similarity	NPC316426
0.7416	Intermediate Similarity	NPC107787
0.7416	Intermediate Similarity	NPC220478
0.7416	Intermediate Similarity	NPC234038
0.7416	Intermediate Similarity	NPC262085
0.7416	Intermediate Similarity	NPC122502
0.7416	Intermediate Similarity	NPC469910
0.7412	Intermediate Similarity	NPC622
0.7412	Intermediate Similarity	NPC276647

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 NPC475481 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	182
0.1-0.2	1657
0.2-0.3	3898
0.3-0.4	2293
0.4-0.5	776
0.5-0.6	283
0.6-0.7	54
0.7-0.8	6
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8068	Intermediate Similarity	NPD6698	Approved
0.8068	Intermediate Similarity	NPD46	Approved
0.7532	Intermediate Similarity	NPD2685	Clinical (unspecified phase)
0.7349	Intermediate Similarity	NPD8039	Approved
0.7303	Intermediate Similarity	NPD1733	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD7154	Phase 3
0.7204	Intermediate Similarity	NPD7983	Approved
0.7174	Intermediate Similarity	NPD1695	Approved
0.7174	Intermediate Similarity	NPD6101	Approved
0.7174	Intermediate Similarity	NPD5764	Clinical (unspecified phase)
0.7128	Intermediate Similarity	NPD5779	Approved
0.7128	Intermediate Similarity	NPD5778	Approved
0.7083	Intermediate Similarity	NPD7839	Suspended
0.7045	Intermediate Similarity	NPD5369	Approved
0.7021	Intermediate Similarity	NPD6411	Approved
0.6966	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD5209	Approved
0.6966	Remote Similarity	NPD4270	Approved
0.6966	Remote Similarity	NPD4269	Approved
0.6932	Remote Similarity	NPD4822	Approved
0.6932	Remote Similarity	NPD4821	Approved
0.6932	Remote Similarity	NPD4820	Approved
0.6932	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6932	Remote Similarity	NPD4819	Approved
0.6915	Remote Similarity	NPD5785	Approved
0.6915	Remote Similarity	NPD7838	Discovery
0.6889	Remote Similarity	NPD5362	Discontinued
0.6848	Remote Similarity	NPD5786	Approved
0.6804	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6796	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6778	Remote Similarity	NPD6435	Approved
0.6762	Remote Similarity	NPD6371	Approved
0.6742	Remote Similarity	NPD4252	Approved
0.6739	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6739	Remote Similarity	NPD5363	Approved
0.6705	Remote Similarity	NPD4268	Approved
0.6705	Remote Similarity	NPD4271	Approved
0.6667	Remote Similarity	NPD6422	Discontinued
0.66	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6559	Remote Similarity	NPD1694	Approved
0.6556	Remote Similarity	NPD5368	Approved
0.6545	Remote Similarity	NPD7115	Discovery
0.6542	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD6648	Approved
0.6531	Remote Similarity	NPD5282	Discontinued
0.6517	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD7637	Suspended
0.6471	Remote Similarity	NPD5344	Discontinued
0.6436	Remote Similarity	NPD4225	Approved
0.6429	Remote Similarity	NPD6399	Phase 3
0.6421	Remote Similarity	NPD4250	Approved
0.6421	Remote Similarity	NPD4251	Approved
0.6415	Remote Similarity	NPD6686	Approved
0.6379	Remote Similarity	NPD8273	Phase 1
0.6344	Remote Similarity	NPD5332	Approved
0.6344	Remote Similarity	NPD5331	Approved
0.6341	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.633	Remote Similarity	NPD6053	Discontinued
0.6327	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD6409	Approved
0.6316	Remote Similarity	NPD4249	Approved
0.6316	Remote Similarity	NPD8516	Approved
0.6316	Remote Similarity	NPD7521	Approved
0.6316	Remote Similarity	NPD7334	Approved
0.6316	Remote Similarity	NPD8515	Approved
0.6316	Remote Similarity	NPD8513	Phase 3
0.6316	Remote Similarity	NPD5330	Approved
0.6316	Remote Similarity	NPD7146	Approved
0.6316	Remote Similarity	NPD6684	Approved
0.6316	Remote Similarity	NPD8517	Approved
0.6304	Remote Similarity	NPD4790	Discontinued
0.6289	Remote Similarity	NPD6051	Approved
0.6289	Remote Similarity	NPD5370	Suspended
0.6277	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6267	Remote Similarity	NPD6927	Phase 3
0.6207	Remote Similarity	NPD7830	Approved
0.6207	Remote Similarity	NPD7642	Approved
0.6207	Remote Similarity	NPD7829	Approved
0.62	Remote Similarity	NPD7900	Approved
0.62	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.619	Remote Similarity	NPD7331	Phase 2
0.6186	Remote Similarity	NPD6903	Approved
0.6186	Remote Similarity	NPD6672	Approved
0.6186	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6186	Remote Similarity	NPD5737	Approved
0.6168	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD5693	Phase 1
0.6117	Remote Similarity	NPD7638	Approved
0.6075	Remote Similarity	NPD6008	Approved
0.6058	Remote Similarity	NPD7640	Approved
0.6058	Remote Similarity	NPD7639	Approved
0.6055	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6053	Remote Similarity	NPD29	Approved
0.6053	Remote Similarity	NPD28	Approved
0.605	Remote Similarity	NPD8074	Phase 3
0.6044	Remote Similarity	NPD4756	Discovery
0.604	Remote Similarity	NPD7748	Approved
0.6034	Remote Similarity	NPD8444	Approved
0.6019	Remote Similarity	NPD6083	Phase 2
0.6019	Remote Similarity	NPD7902	Approved
0.6019	Remote Similarity	NPD6084	Phase 2
0.6	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.598	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.598	Remote Similarity	NPD5695	Phase 3
0.5979	Remote Similarity	NPD6098	Approved
0.5978	Remote Similarity	NPD3732	Approved
0.5966	Remote Similarity	NPD8451	Approved
0.5963	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.596	Remote Similarity	NPD6673	Approved
0.596	Remote Similarity	NPD6904	Approved
0.596	Remote Similarity	NPD6080	Approved
0.5952	Remote Similarity	NPD3197	Phase 1
0.5926	Remote Similarity	NPD5739	Approved
0.5926	Remote Similarity	NPD6675	Approved
0.5926	Remote Similarity	NPD7128	Approved
0.5926	Remote Similarity	NPD6402	Approved
0.5918	Remote Similarity	NPD3573	Approved
0.5917	Remote Similarity	NPD8448	Approved
0.5882	Remote Similarity	NPD7341	Phase 2
0.5856	Remote Similarity	NPD2067	Discontinued
0.5842	Remote Similarity	NPD7515	Phase 2
0.5842	Remote Similarity	NPD6050	Approved
0.5823	Remote Similarity	NPD3196	Approved
0.5823	Remote Similarity	NPD3194	Approved
0.5823	Remote Similarity	NPD3195	Phase 2
0.5823	Remote Similarity	NPD4266	Approved
0.582	Remote Similarity	NPD7319	Approved
0.5818	Remote Similarity	NPD7320	Approved
0.5818	Remote Similarity	NPD6881	Approved
0.5818	Remote Similarity	NPD6899	Approved
0.5814	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.581	Remote Similarity	NPD5696	Approved
0.5783	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD3668	Phase 3
0.5773	Remote Similarity	NPD4786	Approved
0.5773	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5772	Remote Similarity	NPD8392	Approved
0.5772	Remote Similarity	NPD8390	Approved
0.5772	Remote Similarity	NPD8391	Approved
0.5769	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.5766	Remote Similarity	NPD6373	Approved
0.5766	Remote Similarity	NPD6372	Approved
0.575	Remote Similarity	NPD8342	Approved
0.575	Remote Similarity	NPD8341	Approved
0.575	Remote Similarity	NPD8340	Approved
0.575	Remote Similarity	NPD8299	Approved
0.5747	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.5743	Remote Similarity	NPD5692	Phase 3
0.5729	Remote Similarity	NPD3667	Approved
0.5727	Remote Similarity	NPD5697	Approved
0.5727	Remote Similarity	NPD5701	Approved
0.5714	Remote Similarity	NPD7290	Approved
0.5714	Remote Similarity	NPD6883	Approved
0.5714	Remote Similarity	NPD7102	Approved
0.5714	Remote Similarity	NPD368	Approved
0.5702	Remote Similarity	NPD7507	Approved
0.57	Remote Similarity	NPD5208	Approved
0.5696	Remote Similarity	NPD3172	Approved
0.569	Remote Similarity	NPD7500	Approved
0.5686	Remote Similarity	NPD5694	Approved
0.5686	Remote Similarity	NPD8035	Phase 2
0.5686	Remote Similarity	NPD8034	Phase 2
0.567	Remote Similarity	NPD6695	Phase 3
0.5664	Remote Similarity	NPD6617	Approved
0.5664	Remote Similarity	NPD6847	Approved
0.5664	Remote Similarity	NPD8130	Phase 1
0.5664	Remote Similarity	NPD6650	Approved
0.5664	Remote Similarity	NPD6869	Approved
0.5664	Remote Similarity	NPD6649	Approved
0.5658	Remote Similarity	NPD5343	Approved
0.5625	Remote Similarity	NPD6012	Approved
0.5625	Remote Similarity	NPD6013	Approved
0.5625	Remote Similarity	NPD6014	Approved
0.5625	Remote Similarity	NPD6413	Approved
0.5619	Remote Similarity	NPD4792	Clinical (unspecified phase)
0.5619	Remote Similarity	NPD4228	Discovery
0.5614	Remote Similarity	NPD8297	Approved
0.5614	Remote Similarity	NPD6882	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