NPASS Compound

Structure

NPC471796 OpenBabel07101718312D 22 24 0 0 1 0 0 0 0 0999 V2000 5.5049 3.1199 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6775 -1.3216 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5359 -1.8345 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9920 2.2614 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6656 0.3951 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5050 3.1349 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1336 2.7893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2602 2.3023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9771 1.2765 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5469 -0.9242 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3090 0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1037 0.7895 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2379 -0.2014 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3090 0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5509 -0.8346 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9921 2.2764 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2453 1.3024 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1890 -0.5104 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 1.2601 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 2 0 0 0 0 2 17 1 0 0 0 0 3 17 1 0 0 0 0 6 18 1 0 0 0 0 7 8 1 0 0 0 0 7 18 1 0 0 0 0 8 19 1 0 0 0 0 9 12 2 0 0 0 0 9 15 1 0 0 0 0 10 13 1 0 0 0 0 10 18 1 0 0 0 0 11 14 1 0 0 0 0 11 17 1 0 0 0 0 12 19 1 0 0 0 0 13 14 1 0 0 0 0 13 19 1 1 0 0 0 14 20 1 1 0 0 0 15 21 2 0 0 0 0 15 22 1 0 0 0 0 16 12 1 1 0 0 0 16 17 1 0 0 0 0 16 22 1 0 0 0 0 18 4 1 6 0 0 0 19 5 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	304.2
Volume:	329.972
LogP:	3.979
LogD:	3.697
LogS:	-4.61
# Rotatable Bonds:	1
TPSA:	53.6
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.761
Synthetic Accessibility Score:	4.935
Fsp3:	0.684
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.864
MDCK Permeability:	2.4313078029081225e-05
Pgp-inhibitor:	0.909
Pgp-substrate:	0.328
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.035
30% Bioavailability (F30%):	0.02

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.23
Plasma Protein Binding (PPB):	95.82062530517578%
Volume Distribution (VD):	1.283
Pgp-substrate:	8.314447402954102%

ADMET: Metabolism

CYP1A2-inhibitor:	0.052
CYP1A2-substrate:	0.715
CYP2C19-inhibitor:	0.172
CYP2C19-substrate:	0.825
CYP2C9-inhibitor:	0.257
CYP2C9-substrate:	0.85
CYP2D6-inhibitor:	0.175
CYP2D6-substrate:	0.564
CYP3A4-inhibitor:	0.574
CYP3A4-substrate:	0.314

ADMET: Excretion

Clearance (CL):	3.191
Half-life (T1/2):	0.231

ADMET: Toxicity

hERG Blockers:	0.013
Human Hepatotoxicity (H-HT):	0.155
Drug-inuced Liver Injury (DILI):	0.271
AMES Toxicity:	0.029
Rat Oral Acute Toxicity:	0.168
Maximum Recommended Daily Dose:	0.153
Skin Sensitization:	0.119
Carcinogencity:	0.236
Eye Corrosion:	0.019
Eye Irritation:	0.146
Respiratory Toxicity:	0.938

Download Data

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

Natural Product: NPC471796

Natural Product ID:	NPC471796
*Common Name:**	Ebractenoid B
IUPAC Name:	(3aR,6S,6aR,8R,10aR)-8-ethenyl-6-hydroxy-4,4,8,10a-tetramethyl-5,6,6a,7,9,10-hexahydro-3aH-benzo[6,7]cyclohepta[4,6-c]furan-2-one
Synonyms:
Standard InCHIKey:	IJNNVZQLPKGNLI-FUUSMOTLSA-N
Standard InCHI:	InChI=1S/C19H28O3/c1-6-18(4)7-8-19(5)12-9-15(21)22-16(12)17(2,3)11-14(20)13(19)10-18/h6,9,13-14,16,20H,1,7-8,10-11H2,2-5H3/t13-,14-,16-,18+,19-/m0/s1
SMILES:	C=C[C@]1(C)CC[C@@]2([C@@H](C1)[C@@H](O)CC([C@@H]1C2=CC(=O)O1)(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3234213
PubChem CID:	90670336
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001983] Dihydrofurans [CHEMONTID:0001982] Furanones [CHEMONTID:0002223] Butenolides

*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
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[16792421]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21534540]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	whole plants	Panshi, Jilin Province, China	2009-JUN	PMID[21534540]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[24660966]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25453801]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26702644]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[28383891]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[29148766]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31184480]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	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	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell Line	RAW264.7	Mus musculus	IC50	=	6490.0	nM	PMID[507802]
NPT113	Cell Line	RAW264.7	Mus musculus	IC50	>	20000.0	nM	PMID[507803]

☑ 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 NPC471796 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	178
0.1-0.2	1191
0.2-0.3	4584
0.3-0.4	12459
0.4-0.5	10879
0.5-0.6	7538
0.6-0.7	5078
0.7-0.8	769
0.8-0.85	18
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9512	High Similarity	NPC471795
0.8721	High Similarity	NPC471219
0.8667	High Similarity	NPC105490
0.8588	High Similarity	NPC311070
0.8556	High Similarity	NPC7349
0.837	Intermediate Similarity	NPC276110
0.8295	Intermediate Similarity	NPC131813
0.8222	Intermediate Similarity	NPC470734
0.8211	Intermediate Similarity	NPC324841
0.8202	Intermediate Similarity	NPC312561
0.8191	Intermediate Similarity	NPC51499
0.8182	Intermediate Similarity	NPC42586
0.8182	Intermediate Similarity	NPC473251
0.8161	Intermediate Similarity	NPC23748
0.8161	Intermediate Similarity	NPC42476
0.8161	Intermediate Similarity	NPC472377
0.8132	Intermediate Similarity	NPC78973
0.8132	Intermediate Similarity	NPC209816
0.8132	Intermediate Similarity	NPC310479
0.8132	Intermediate Similarity	NPC182136
0.8125	Intermediate Similarity	NPC11974
0.8118	Intermediate Similarity	NPC110373
0.8118	Intermediate Similarity	NPC242767
0.8118	Intermediate Similarity	NPC5908
0.8118	Intermediate Similarity	NPC80471
0.8111	Intermediate Similarity	NPC472810
0.8111	Intermediate Similarity	NPC472809
0.8105	Intermediate Similarity	NPC278673
0.8105	Intermediate Similarity	NPC275086
0.8105	Intermediate Similarity	NPC325229
0.8085	Intermediate Similarity	NPC165632
0.8068	Intermediate Similarity	NPC102048
0.8068	Intermediate Similarity	NPC32223
0.8065	Intermediate Similarity	NPC469491
0.8043	Intermediate Similarity	NPC249034
0.8043	Intermediate Similarity	NPC473675
0.8043	Intermediate Similarity	NPC234335
0.8041	Intermediate Similarity	NPC475038
0.8041	Intermediate Similarity	NPC109195
0.8022	Intermediate Similarity	NPC261320
0.8022	Intermediate Similarity	NPC5509
0.8021	Intermediate Similarity	NPC477716
0.8021	Intermediate Similarity	NPC54705
0.8021	Intermediate Similarity	NPC477721
0.8021	Intermediate Similarity	NPC38855
0.8	Intermediate Similarity	NPC477718
0.8	Intermediate Similarity	NPC184737
0.8	Intermediate Similarity	NPC477719
0.8	Intermediate Similarity	NPC98112
0.7978	Intermediate Similarity	NPC106416
0.7978	Intermediate Similarity	NPC86316
0.7978	Intermediate Similarity	NPC30984
0.7959	Intermediate Similarity	NPC472821
0.7959	Intermediate Similarity	NPC281378
0.7959	Intermediate Similarity	NPC160583
0.7957	Intermediate Similarity	NPC115021
0.7957	Intermediate Similarity	NPC152778
0.7957	Intermediate Similarity	NPC472640
0.7957	Intermediate Similarity	NPC205034
0.7957	Intermediate Similarity	NPC162615
0.7957	Intermediate Similarity	NPC53555
0.7957	Intermediate Similarity	NPC472641
0.7955	Intermediate Similarity	NPC49208
0.7955	Intermediate Similarity	NPC474809
0.7938	Intermediate Similarity	NPC198992
0.7938	Intermediate Similarity	NPC471412
0.7938	Intermediate Similarity	NPC268829
0.7938	Intermediate Similarity	NPC472554
0.7938	Intermediate Similarity	NPC477717
0.7938	Intermediate Similarity	NPC25177
0.7938	Intermediate Similarity	NPC247701
0.7938	Intermediate Similarity	NPC222875
0.7938	Intermediate Similarity	NPC295110
0.7935	Intermediate Similarity	NPC281942
0.7935	Intermediate Similarity	NPC221111
0.7935	Intermediate Similarity	NPC232426
0.7935	Intermediate Similarity	NPC220216
0.7935	Intermediate Similarity	NPC280149
0.7917	Intermediate Similarity	NPC222303
0.7912	Intermediate Similarity	NPC472378
0.7912	Intermediate Similarity	NPC291665
0.7895	Intermediate Similarity	NPC29952
0.7895	Intermediate Similarity	NPC134072
0.7895	Intermediate Similarity	NPC234993
0.7872	Intermediate Similarity	NPC57117
0.7872	Intermediate Similarity	NPC140277
0.7872	Intermediate Similarity	NPC469697
0.7872	Intermediate Similarity	NPC104925
0.7872	Intermediate Similarity	NPC298973
0.7872	Intermediate Similarity	NPC470255
0.7857	Intermediate Similarity	NPC476081
0.7857	Intermediate Similarity	NPC11956
0.7857	Intermediate Similarity	NPC472552
0.7857	Intermediate Similarity	NPC469606
0.7857	Intermediate Similarity	NPC273005
0.7857	Intermediate Similarity	NPC162973
0.7857	Intermediate Similarity	NPC31058
0.7849	Intermediate Similarity	NPC477574
0.7849	Intermediate Similarity	NPC124374
0.7849	Intermediate Similarity	NPC78594
0.7849	Intermediate Similarity	NPC472814
0.7849	Intermediate Similarity	NPC141831
0.7849	Intermediate Similarity	NPC329842
0.7849	Intermediate Similarity	NPC472811
0.7849	Intermediate Similarity	NPC177037
0.7841	Intermediate Similarity	NPC224455
0.7841	Intermediate Similarity	NPC471218
0.7835	Intermediate Similarity	NPC251680
0.7835	Intermediate Similarity	NPC476767
0.7835	Intermediate Similarity	NPC16601
0.7835	Intermediate Similarity	NPC471413
0.7826	Intermediate Similarity	NPC174342
0.7826	Intermediate Similarity	NPC50488
0.7826	Intermediate Similarity	NPC474396
0.7826	Intermediate Similarity	NPC246028
0.7816	Intermediate Similarity	NPC469802
0.7812	Intermediate Similarity	NPC205143
0.7802	Intermediate Similarity	NPC471779
0.78	Intermediate Similarity	NPC220217
0.78	Intermediate Similarity	NPC119855
0.78	Intermediate Similarity	NPC172867
0.78	Intermediate Similarity	NPC218158
0.7789	Intermediate Similarity	NPC476720
0.7789	Intermediate Similarity	NPC472441
0.7778	Intermediate Similarity	NPC45897
0.7778	Intermediate Similarity	NPC120009
0.7778	Intermediate Similarity	NPC187302
0.7778	Intermediate Similarity	NPC23584
0.7778	Intermediate Similarity	NPC65661
0.7778	Intermediate Similarity	NPC471938
0.7778	Intermediate Similarity	NPC474013
0.7778	Intermediate Similarity	NPC10232
0.7778	Intermediate Similarity	NPC119001
0.7778	Intermediate Similarity	NPC189588
0.7778	Intermediate Similarity	NPC97487
0.7778	Intermediate Similarity	NPC196471
0.7766	Intermediate Similarity	NPC110022
0.7766	Intermediate Similarity	NPC99653
0.7766	Intermediate Similarity	NPC472812
0.7766	Intermediate Similarity	NPC475657
0.7766	Intermediate Similarity	NPC139692
0.7753	Intermediate Similarity	NPC477124
0.7753	Intermediate Similarity	NPC193198
0.7742	Intermediate Similarity	NPC51486
0.7742	Intermediate Similarity	NPC472642
0.7732	Intermediate Similarity	NPC23364
0.7727	Intermediate Similarity	NPC475944
0.7723	Intermediate Similarity	NPC109376
0.7723	Intermediate Similarity	NPC475074
0.7723	Intermediate Similarity	NPC471205
0.7717	Intermediate Similarity	NPC93411
0.7717	Intermediate Similarity	NPC106332
0.7717	Intermediate Similarity	NPC474629
0.7708	Intermediate Similarity	NPC473153
0.7708	Intermediate Similarity	NPC475380
0.7708	Intermediate Similarity	NPC162346
0.7708	Intermediate Similarity	NPC209297
0.7708	Intermediate Similarity	NPC16967
0.7708	Intermediate Similarity	NPC194132
0.7701	Intermediate Similarity	NPC139712
0.7701	Intermediate Similarity	NPC226226
0.7701	Intermediate Similarity	NPC55304
0.77	Intermediate Similarity	NPC471937
0.77	Intermediate Similarity	NPC200861
0.7692	Intermediate Similarity	NPC329692
0.7684	Intermediate Similarity	NPC472360
0.7684	Intermediate Similarity	NPC477722
0.7684	Intermediate Similarity	NPC161998
0.7684	Intermediate Similarity	NPC472416
0.7684	Intermediate Similarity	NPC250075
0.7684	Intermediate Similarity	NPC191521
0.7684	Intermediate Similarity	NPC201725
0.7677	Intermediate Similarity	NPC472815
0.7677	Intermediate Similarity	NPC471914
0.7677	Intermediate Similarity	NPC471363
0.7677	Intermediate Similarity	NPC238397
0.7674	Intermediate Similarity	NPC262747
0.7674	Intermediate Similarity	NPC189206
0.7674	Intermediate Similarity	NPC477203
0.7667	Intermediate Similarity	NPC222634
0.7667	Intermediate Similarity	NPC471302
0.7667	Intermediate Similarity	NPC96055
0.7667	Intermediate Similarity	NPC474693
0.7667	Intermediate Similarity	NPC471301
0.766	Intermediate Similarity	NPC303697
0.766	Intermediate Similarity	NPC477122
0.766	Intermediate Similarity	NPC72845
0.7653	Intermediate Similarity	NPC47024
0.7653	Intermediate Similarity	NPC20113
0.7653	Intermediate Similarity	NPC477972
0.7653	Intermediate Similarity	NPC161527
0.7653	Intermediate Similarity	NPC477968
0.7653	Intermediate Similarity	NPC477971
0.7653	Intermediate Similarity	NPC219285
0.7653	Intermediate Similarity	NPC228251
0.7647	Intermediate Similarity	NPC470024
0.7647	Intermediate Similarity	NPC38948
0.7647	Intermediate Similarity	NPC224660
0.764	Intermediate Similarity	NPC256112
0.764	Intermediate Similarity	NPC471298

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 NPC471796 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	157
0.1-0.2	1530
0.2-0.3	3942
0.3-0.4	2432
0.4-0.5	680
0.5-0.6	279
0.6-0.7	125
0.7-0.8	5
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
0.7917	Intermediate Similarity	NPD7638	Approved
0.7835	Intermediate Similarity	NPD7639	Approved
0.7835	Intermediate Similarity	NPD7640	Approved
0.7476	Intermediate Similarity	NPD6686	Approved
0.7444	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.7228	Intermediate Similarity	NPD5344	Discontinued
0.72	Intermediate Similarity	NPD4225	Approved
0.7188	Intermediate Similarity	NPD7838	Discovery
0.7157	Intermediate Similarity	NPD7632	Discontinued
0.7097	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.7075	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7071	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD7327	Approved
0.7027	Intermediate Similarity	NPD7328	Approved
0.7021	Intermediate Similarity	NPD1694	Approved
0.701	Intermediate Similarity	NPD6698	Approved
0.701	Intermediate Similarity	NPD46	Approved
0.6964	Remote Similarity	NPD7516	Approved
0.6961	Remote Similarity	NPD6648	Approved
0.6939	Remote Similarity	NPD7637	Suspended
0.6907	Remote Similarity	NPD6051	Approved
0.6903	Remote Similarity	NPD8377	Approved
0.6903	Remote Similarity	NPD8294	Approved
0.6881	Remote Similarity	NPD6053	Discontinued
0.6852	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD6371	Approved
0.6842	Remote Similarity	NPD8379	Approved
0.6842	Remote Similarity	NPD8378	Approved
0.6842	Remote Similarity	NPD8033	Approved
0.6842	Remote Similarity	NPD8380	Approved
0.6842	Remote Similarity	NPD8296	Approved
0.6842	Remote Similarity	NPD7503	Approved
0.6842	Remote Similarity	NPD8335	Approved
0.6786	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6771	Remote Similarity	NPD7146	Approved
0.6771	Remote Similarity	NPD7521	Approved
0.6771	Remote Similarity	NPD7334	Approved
0.6771	Remote Similarity	NPD6684	Approved
0.6771	Remote Similarity	NPD5330	Approved
0.6771	Remote Similarity	NPD6409	Approved
0.6737	Remote Similarity	NPD3133	Approved
0.6737	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6737	Remote Similarity	NPD3665	Phase 1
0.6737	Remote Similarity	NPD3666	Approved
0.67	Remote Similarity	NPD6399	Phase 3
0.6699	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5785	Approved
0.6667	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6634	Remote Similarity	NPD7748	Approved
0.6633	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6633	Remote Similarity	NPD6903	Approved
0.6632	Remote Similarity	NPD6695	Phase 3
0.661	Remote Similarity	NPD7507	Approved
0.6602	Remote Similarity	NPD6084	Phase 2
0.6602	Remote Similarity	NPD7902	Approved
0.6602	Remote Similarity	NPD6083	Phase 2
0.66	Remote Similarity	NPD7515	Phase 2
0.6598	Remote Similarity	NPD3618	Phase 1
0.6598	Remote Similarity	NPD4249	Approved
0.6593	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.6574	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6574	Remote Similarity	NPD5697	Approved
0.6574	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6574	Remote Similarity	NPD6412	Phase 2
0.6569	Remote Similarity	NPD5695	Phase 3
0.6566	Remote Similarity	NPD1695	Approved
0.6559	Remote Similarity	NPD4195	Approved
0.6559	Remote Similarity	NPD6929	Approved
0.6535	Remote Similarity	NPD5778	Approved
0.6535	Remote Similarity	NPD5779	Approved
0.6531	Remote Similarity	NPD4250	Approved
0.6531	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.6531	Remote Similarity	NPD4251	Approved
0.6526	Remote Similarity	NPD5209	Approved
0.6526	Remote Similarity	NPD3667	Approved
0.6518	Remote Similarity	NPD4632	Approved
0.6514	Remote Similarity	NPD6881	Approved
0.6514	Remote Similarity	NPD6899	Approved
0.6514	Remote Similarity	NPD6011	Approved
0.6491	Remote Similarity	NPD7115	Discovery
0.6489	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6489	Remote Similarity	NPD7525	Registered
0.6489	Remote Similarity	NPD7514	Phase 3
0.6489	Remote Similarity	NPD6931	Approved
0.6489	Remote Similarity	NPD6930	Phase 2
0.6489	Remote Similarity	NPD7332	Phase 2
0.6484	Remote Similarity	NPD6942	Approved
0.6484	Remote Similarity	NPD8039	Approved
0.6484	Remote Similarity	NPD7339	Approved
0.6481	Remote Similarity	NPD7128	Approved
0.6481	Remote Similarity	NPD5739	Approved
0.6481	Remote Similarity	NPD6402	Approved
0.6481	Remote Similarity	NPD6675	Approved
0.6471	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD5282	Discontinued
0.6465	Remote Similarity	NPD6672	Approved
0.6465	Remote Similarity	NPD5737	Approved
0.6455	Remote Similarity	NPD6013	Approved
0.6455	Remote Similarity	NPD6014	Approved
0.6455	Remote Similarity	NPD6012	Approved
0.6452	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6452	Remote Similarity	NPD7145	Approved
0.6446	Remote Similarity	NPD7319	Approved
0.6436	Remote Similarity	NPD5693	Phase 1
0.6436	Remote Similarity	NPD5281	Approved
0.6436	Remote Similarity	NPD5284	Approved
0.6436	Remote Similarity	NPD6079	Approved
0.6429	Remote Similarity	NPD4623	Approved
0.6429	Remote Similarity	NPD4519	Discontinued
0.6429	Remote Similarity	NPD5279	Phase 3
0.6422	Remote Similarity	NPD5701	Approved
0.6421	Remote Similarity	NPD6902	Approved
0.64	Remote Similarity	NPD5328	Approved
0.6396	Remote Similarity	NPD7102	Approved
0.6396	Remote Similarity	NPD7290	Approved
0.6396	Remote Similarity	NPD6883	Approved
0.6392	Remote Similarity	NPD4786	Approved
0.6383	Remote Similarity	NPD7645	Phase 2
0.6381	Remote Similarity	NPD5696	Approved
0.6374	Remote Similarity	NPD6926	Approved
0.6374	Remote Similarity	NPD6924	Approved
0.6373	Remote Similarity	NPD4202	Approved
0.6364	Remote Similarity	NPD7320	Approved
0.6364	Remote Similarity	NPD7750	Discontinued
0.6364	Remote Similarity	NPD7524	Approved
0.6348	Remote Similarity	NPD6009	Approved
0.6344	Remote Similarity	NPD6932	Approved
0.6344	Remote Similarity	NPD6925	Approved
0.6344	Remote Similarity	NPD5776	Phase 2
0.6339	Remote Similarity	NPD8130	Phase 1
0.6339	Remote Similarity	NPD6650	Approved
0.6339	Remote Similarity	NPD6617	Approved
0.6339	Remote Similarity	NPD6847	Approved
0.6339	Remote Similarity	NPD6649	Approved
0.6339	Remote Similarity	NPD6869	Approved
0.633	Remote Similarity	NPD6008	Approved
0.6325	Remote Similarity	NPD6319	Approved
0.6316	Remote Similarity	NPD4820	Approved
0.6316	Remote Similarity	NPD4822	Approved
0.6316	Remote Similarity	NPD4821	Approved
0.6316	Remote Similarity	NPD4819	Approved
0.6311	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6311	Remote Similarity	NPD7900	Approved
0.6306	Remote Similarity	NPD6372	Approved
0.6306	Remote Similarity	NPD6373	Approved
0.6304	Remote Similarity	NPD8264	Approved
0.6289	Remote Similarity	NPD5362	Discontinued
0.6289	Remote Similarity	NPD7154	Phase 3
0.6283	Remote Similarity	NPD6882	Approved
0.6283	Remote Similarity	NPD8297	Approved
0.6277	Remote Similarity	NPD4268	Approved
0.6277	Remote Similarity	NPD4271	Approved
0.6277	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6275	Remote Similarity	NPD6411	Approved
0.6275	Remote Similarity	NPD7983	Approved
0.6271	Remote Similarity	NPD5983	Phase 2
0.6238	Remote Similarity	NPD4753	Phase 2
0.6237	Remote Similarity	NPD6933	Approved
0.6235	Remote Similarity	NPD4193	Approved
0.6235	Remote Similarity	NPD368	Approved
0.6235	Remote Similarity	NPD4192	Approved
0.6235	Remote Similarity	NPD4191	Approved
0.6235	Remote Similarity	NPD4194	Approved
0.6222	Remote Similarity	NPD7143	Approved
0.6222	Remote Similarity	NPD7144	Approved
0.6216	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6204	Remote Similarity	NPD5211	Phase 2
0.62	Remote Similarity	NPD3573	Approved
0.6195	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.619	Remote Similarity	NPD4792	Clinical (unspecified phase)
0.619	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.619	Remote Similarity	NPD5221	Approved
0.619	Remote Similarity	NPD5222	Approved
0.6186	Remote Similarity	NPD6435	Approved
0.6186	Remote Similarity	NPD4223	Phase 3
0.6186	Remote Similarity	NPD4221	Approved
0.6176	Remote Similarity	NPD5207	Approved
0.6168	Remote Similarity	NPD5286	Approved
0.6168	Remote Similarity	NPD5285	Approved
0.6168	Remote Similarity	NPD4696	Approved
0.6167	Remote Similarity	NPD7604	Phase 2
0.6162	Remote Similarity	NPD5363	Approved
0.6162	Remote Similarity	NPD6893	Approved
0.6162	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6154	Remote Similarity	NPD7152	Approved
0.6154	Remote Similarity	NPD7151	Approved
0.6154	Remote Similarity	NPD7150	Approved
0.6146	Remote Similarity	NPD7509	Discontinued
0.6139	Remote Similarity	NPD5208	Approved
0.6132	Remote Similarity	NPD4755	Approved
0.6132	Remote Similarity	NPD5173	Approved
0.6122	Remote Similarity	NPD5332	Approved
0.6122	Remote Similarity	NPD5331	Approved
0.6117	Remote Similarity	NPD5694	Approved
0.6117	Remote Similarity	NPD8035	Phase 2
0.6117	Remote Similarity	NPD8034	Phase 2
0.6117	Remote Similarity	NPD7087	Discontinued
0.6116	Remote Similarity	NPD7492	Approved
0.6111	Remote Similarity	NPD6922	Approved
0.6111	Remote Similarity	NPD5223	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