NPASS Compound

Structure

NPC235685 OpenBabel07101719152D 26 30 0 0 0 0 0 0 0 0999 V2000 6.5599 -0.5352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2272 -0.2670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0932 0.2330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3612 0.2330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0932 1.2330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6036 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6254 -1.1590 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2872 -1.1590 0.0000 C 0 0 0 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 4.2435 0.7431 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0248 2.8157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9126 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3612 1.2330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9563 -0.4158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9563 -0.4158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6180 1.9021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2272 1.7330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2653 0.5352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6473 0.5352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6691 0.7431 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3601 1.6942 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.0193 2.7111 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.4563 1.1230 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0292 2.4373 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8907 0.2079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 26 1 0 0 0 0 2 3 2 0 0 0 0 2 4 1 0 0 0 0 3 5 1 0 0 0 0 4 13 2 0 0 0 0 5 17 2 0 0 0 0 6 7 2 0 0 0 0 6 12 1 0 0 0 0 7 14 1 0 0 0 0 8 9 1 0 0 0 0 8 15 2 0 0 0 0 9 22 2 0 0 0 0 10 12 2 0 0 0 0 10 18 1 0 0 0 0 11 16 2 0 0 0 0 11 23 1 0 0 0 0 12 26 1 0 0 0 0 13 16 1 0 0 0 0 13 17 1 0 0 0 0 14 15 1 0 0 0 0 14 18 2 0 0 0 0 15 19 1 0 0 0 0 16 21 1 0 0 0 0 17 23 1 0 0 0 0 18 24 1 0 0 0 0 19 20 2 0 0 0 0 19 24 1 0 0 0 0 20 21 1 0 0 0 0 20 22 1 0 0 0 0 21 25 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	341.12
Volume:	350.56
LogP:	4.246
LogD:	3.703
LogS:	-6.048
# Rotatable Bonds:	3
TPSA:	70.77
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.477
Synthetic Accessibility Score:	2.364
Fsp3:	0.048
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:	-5.225
MDCK Permeability:	5.843693088536384e-06
Pgp-inhibitor:	0.628
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.333
Plasma Protein Binding (PPB):	97.73331451416016%
Volume Distribution (VD):	0.907
Pgp-substrate:	2.134263038635254%

ADMET: Metabolism

CYP1A2-inhibitor:	0.98
CYP1A2-substrate:	0.727
CYP2C19-inhibitor:	0.886
CYP2C19-substrate:	0.068
CYP2C9-inhibitor:	0.854
CYP2C9-substrate:	0.938
CYP2D6-inhibitor:	0.767
CYP2D6-substrate:	0.887
CYP3A4-inhibitor:	0.926
CYP3A4-substrate:	0.187

ADMET: Excretion

Clearance (CL):	4.885
Half-life (T1/2):	0.151

ADMET: Toxicity

hERG Blockers:	0.284
Human Hepatotoxicity (H-HT):	0.934
Drug-inuced Liver Injury (DILI):	0.962
AMES Toxicity:	0.958
Rat Oral Acute Toxicity:	0.845
Maximum Recommended Daily Dose:	0.968
Skin Sensitization:	0.59
Carcinogencity:	0.485
Eye Corrosion:	0.003
Eye Irritation:	0.71
Respiratory Toxicity:	0.958

Download Data

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

Natural Product: NPC235685

Natural Product ID:	NPC235685
*Common Name:**	Trigonostemine A
IUPAC Name:	1H-indol-3-yl-(7-methoxy-9H-pyrido[3,4-b]indol-1-yl)methanone
Synonyms:	Trigonostemine A
Standard InCHIKey:	PGGWEUVCQQRYQR-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C21H15N3O2/c1-26-12-6-7-14-15-8-9-22-20(19(15)24-18(14)10-12)21(25)16-11-23-17-5-3-2-4-13(16)17/h2-11,23-24H,1H3
SMILES:	COc1ccc2c(c1)[nH]c1c2ccnc1C(=O)c1c[nH]c2c1cccc2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1957108
PubChem CID:	57345601
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001140] Harmala alkaloids

*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
NPO503	Trigonostemon lii	Species	Euphorbiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[22342628]
NPO503	Trigonostemon lii	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	5

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	13390.0	nM	PMID[528125]
NPT659	Cell Line	SMMC-7721	Homo sapiens	IC50	=	22410.0	nM	PMID[528125]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	23900.0	nM	PMID[528125]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	5300.0	nM	PMID[528125]
NPT660	Cell Line	SW480	Homo sapiens	IC50	=	4860.0	nM	PMID[528125]

☑ 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 NPC235685 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	683
0.1-0.2	4273
0.2-0.3	12813
0.3-0.4	7708
0.4-0.5	12526
0.5-0.6	2087
0.6-0.7	1983
0.7-0.8	557
0.8-0.85	45
0.85-0.9	14
0.9-0.95	5
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9952	High Similarity	NPC101350
0.9474	High Similarity	NPC122436
0.9409	High Similarity	NPC63971
0.9409	High Similarity	NPC91868
0.912	High Similarity	NPC260434
0.8745	High Similarity	NPC53534
0.8733	High Similarity	NPC207686
0.8704	High Similarity	NPC323969
0.8632	High Similarity	NPC123976
0.8632	High Similarity	NPC167860
0.8578	High Similarity	NPC60621
0.8565	High Similarity	NPC27041
0.8523	High Similarity	NPC152620
0.8517	High Similarity	NPC232727
0.8478	Intermediate Similarity	NPC178858
0.8468	Intermediate Similarity	NPC258048
0.8416	Intermediate Similarity	NPC229893
0.8402	Intermediate Similarity	NPC213530
0.8402	Intermediate Similarity	NPC193267
0.8348	Intermediate Similarity	NPC471762
0.831	Intermediate Similarity	NPC285558
0.8304	Intermediate Similarity	NPC148889
0.8241	Intermediate Similarity	NPC174758
0.8238	Intermediate Similarity	NPC196718
0.8235	Intermediate Similarity	NPC63109
0.8227	Intermediate Similarity	NPC305984
0.8194	Intermediate Similarity	NPC266249
0.8186	Intermediate Similarity	NPC194740
0.8186	Intermediate Similarity	NPC66777
0.8182	Intermediate Similarity	NPC326422
0.8158	Intermediate Similarity	NPC102593
0.8119	Intermediate Similarity	NPC123839
0.8108	Intermediate Similarity	NPC264285
0.81	Intermediate Similarity	NPC322064
0.81	Intermediate Similarity	NPC170114
0.8087	Intermediate Similarity	NPC182222
0.8079	Intermediate Similarity	NPC279189
0.8079	Intermediate Similarity	NPC200553
0.8065	Intermediate Similarity	NPC183777
0.8054	Intermediate Similarity	NPC470549
0.8045	Intermediate Similarity	NPC118940
0.8037	Intermediate Similarity	NPC176538
0.8036	Intermediate Similarity	NPC276657
0.8018	Intermediate Similarity	NPC274982
0.8	Intermediate Similarity	NPC49547
0.7991	Intermediate Similarity	NPC174672
0.7983	Intermediate Similarity	NPC26543
0.7982	Intermediate Similarity	NPC74575
0.7982	Intermediate Similarity	NPC249583
0.7982	Intermediate Similarity	NPC4687
0.7974	Intermediate Similarity	NPC162002
0.7966	Intermediate Similarity	NPC78609
0.7965	Intermediate Similarity	NPC16352
0.7955	Intermediate Similarity	NPC470020
0.7948	Intermediate Similarity	NPC314954
0.794	Intermediate Similarity	NPC15801
0.7937	Intermediate Similarity	NPC36405
0.7931	Intermediate Similarity	NPC174489
0.793	Intermediate Similarity	NPC322482
0.7926	Intermediate Similarity	NPC317701
0.7922	Intermediate Similarity	NPC469554
0.792	Intermediate Similarity	NPC310118
0.7908	Intermediate Similarity	NPC165964
0.7904	Intermediate Similarity	NPC157931
0.7897	Intermediate Similarity	NPC473187
0.789	Intermediate Similarity	NPC132539
0.7883	Intermediate Similarity	NPC110182
0.787	Intermediate Similarity	NPC19872
0.7867	Intermediate Similarity	NPC473041
0.7867	Intermediate Similarity	NPC303658
0.7863	Intermediate Similarity	NPC240384
0.7863	Intermediate Similarity	NPC26641
0.7845	Intermediate Similarity	NPC101543
0.7838	Intermediate Similarity	NPC87413
0.7826	Intermediate Similarity	NPC478078
0.7815	Intermediate Similarity	NPC208522
0.7809	Intermediate Similarity	NPC77101
0.7803	Intermediate Similarity	NPC308137
0.7803	Intermediate Similarity	NPC310211
0.7798	Intermediate Similarity	NPC295898
0.7797	Intermediate Similarity	NPC37152
0.7783	Intermediate Similarity	NPC82548
0.7783	Intermediate Similarity	NPC470018
0.7778	Intermediate Similarity	NPC97902
0.7778	Intermediate Similarity	NPC148183
0.7778	Intermediate Similarity	NPC152768
0.7778	Intermediate Similarity	NPC303374
0.7768	Intermediate Similarity	NPC236668
0.7763	Intermediate Similarity	NPC245816
0.7763	Intermediate Similarity	NPC476138
0.7755	Intermediate Similarity	NPC74619
0.7753	Intermediate Similarity	NPC74360
0.7749	Intermediate Similarity	NPC110151
0.7746	Intermediate Similarity	NPC138370
0.7743	Intermediate Similarity	NPC169402
0.7742	Intermediate Similarity	NPC81535
0.7742	Intermediate Similarity	NPC74413
0.7739	Intermediate Similarity	NPC21638
0.7735	Intermediate Similarity	NPC141053
0.7733	Intermediate Similarity	NPC146976
0.7733	Intermediate Similarity	NPC116238
0.7718	Intermediate Similarity	NPC270515
0.7717	Intermediate Similarity	NPC260900
0.7712	Intermediate Similarity	NPC472061
0.771	Intermediate Similarity	NPC324149
0.7706	Intermediate Similarity	NPC121772
0.7703	Intermediate Similarity	NPC191415
0.7692	Intermediate Similarity	NPC175602
0.7686	Intermediate Similarity	NPC198503
0.7685	Intermediate Similarity	NPC13880
0.7682	Intermediate Similarity	NPC223427
0.7675	Intermediate Similarity	NPC269270
0.7668	Intermediate Similarity	NPC185782
0.7668	Intermediate Similarity	NPC61038
0.7655	Intermediate Similarity	NPC477979
0.7644	Intermediate Similarity	NPC26679
0.7644	Intermediate Similarity	NPC219087
0.7644	Intermediate Similarity	NPC264176
0.7642	Intermediate Similarity	NPC150239
0.7642	Intermediate Similarity	NPC14686
0.7637	Intermediate Similarity	NPC184680
0.7634	Intermediate Similarity	NPC471304
0.7632	Intermediate Similarity	NPC247803
0.7632	Intermediate Similarity	NPC46561
0.7631	Intermediate Similarity	NPC132385
0.763	Intermediate Similarity	NPC84478
0.7627	Intermediate Similarity	NPC39370
0.7626	Intermediate Similarity	NPC329747
0.7623	Intermediate Similarity	NPC287208
0.7623	Intermediate Similarity	NPC39679
0.7617	Intermediate Similarity	NPC473186
0.7615	Intermediate Similarity	NPC67288
0.7613	Intermediate Similarity	NPC472064
0.7611	Intermediate Similarity	NPC476287
0.7611	Intermediate Similarity	NPC469592
0.7611	Intermediate Similarity	NPC471080
0.7605	Intermediate Similarity	NPC470785
0.7605	Intermediate Similarity	NPC470784
0.7602	Intermediate Similarity	NPC53144
0.7602	Intermediate Similarity	NPC478083
0.76	Intermediate Similarity	NPC208284
0.76	Intermediate Similarity	NPC82370
0.7598	Intermediate Similarity	NPC208084
0.7597	Intermediate Similarity	NPC257851
0.7595	Intermediate Similarity	NPC477549
0.7593	Intermediate Similarity	NPC81939
0.7577	Intermediate Similarity	NPC237740
0.7576	Intermediate Similarity	NPC210434
0.7576	Intermediate Similarity	NPC216612
0.7576	Intermediate Similarity	NPC220851
0.757	Intermediate Similarity	NPC296527
0.7569	Intermediate Similarity	NPC227582
0.7568	Intermediate Similarity	NPC470500
0.7565	Intermediate Similarity	NPC174760
0.7563	Intermediate Similarity	NPC470022
0.7562	Intermediate Similarity	NPC475666
0.756	Intermediate Similarity	NPC284775
0.7556	Intermediate Similarity	NPC11464
0.7545	Intermediate Similarity	NPC171787
0.7545	Intermediate Similarity	NPC315957
0.7535	Intermediate Similarity	NPC76748
0.7534	Intermediate Similarity	NPC472065
0.7534	Intermediate Similarity	NPC300156
0.7534	Intermediate Similarity	NPC45190
0.7534	Intermediate Similarity	NPC474916
0.7533	Intermediate Similarity	NPC207866
0.7523	Intermediate Similarity	NPC134848
0.7523	Intermediate Similarity	NPC79356
0.7523	Intermediate Similarity	NPC102592
0.7522	Intermediate Similarity	NPC288987
0.7521	Intermediate Similarity	NPC192712
0.7521	Intermediate Similarity	NPC295228
0.752	Intermediate Similarity	NPC244543
0.7512	Intermediate Similarity	NPC307963
0.75	Intermediate Similarity	NPC284338
0.75	Intermediate Similarity	NPC102755
0.75	Intermediate Similarity	NPC267853
0.75	Intermediate Similarity	NPC92111
0.75	Intermediate Similarity	NPC476460
0.7489	Intermediate Similarity	NPC475070
0.7489	Intermediate Similarity	NPC267928
0.7489	Intermediate Similarity	NPC472099
0.7479	Intermediate Similarity	NPC253675
0.7479	Intermediate Similarity	NPC24370
0.7479	Intermediate Similarity	NPC319232
0.7478	Intermediate Similarity	NPC96321
0.7478	Intermediate Similarity	NPC469594
0.7478	Intermediate Similarity	NPC5145
0.7477	Intermediate Similarity	NPC472063
0.7477	Intermediate Similarity	NPC472069
0.7477	Intermediate Similarity	NPC472062
0.747	Intermediate Similarity	NPC216369
0.7468	Intermediate Similarity	NPC244897
0.7468	Intermediate Similarity	NPC132329
0.7467	Intermediate Similarity	NPC8022
0.7467	Intermediate Similarity	NPC470799
0.7466	Intermediate Similarity	NPC252338
0.7458	Intermediate Similarity	NPC326363
0.7458	Intermediate Similarity	NPC278525
0.7454	Intermediate Similarity	NPC324091

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 NPC235685 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	379
0.1-0.2	643
0.2-0.3	857
0.3-0.4	1643
0.4-0.5	2573
0.5-0.6	1888
0.6-0.7	1052
0.7-0.8	109
0.8-0.85	6
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8502	High Similarity	NPD2921	Clinical (unspecified phase)
0.8448	Intermediate Similarity	NPD5482	Discontinued
0.8355	Intermediate Similarity	NPD5483	Clinical (unspecified phase)
0.8281	Intermediate Similarity	NPD6242	Discontinued
0.8147	Intermediate Similarity	NPD6790	Phase 1
0.8033	Intermediate Similarity	NPD5450	Discontinued
0.8017	Intermediate Similarity	NPD4958	Clinical (unspecified phase)
0.7945	Intermediate Similarity	NPD2510	Approved
0.7945	Intermediate Similarity	NPD2509	Approved
0.7941	Intermediate Similarity	NPD4558	Phase 2
0.7821	Intermediate Similarity	NPD3006	Discontinued
0.7788	Intermediate Similarity	NPD4429	Discontinued
0.7778	Intermediate Similarity	NPD3393	Approved
0.7778	Intermediate Similarity	NPD3389	Approved
0.7778	Intermediate Similarity	NPD3394	Approved
0.7749	Intermediate Similarity	NPD3259	Approved
0.7709	Intermediate Similarity	NPD5632	Approved
0.7703	Intermediate Similarity	NPD5658	Approved
0.7682	Intermediate Similarity	NPD5479	Discontinued
0.7682	Intermediate Similarity	NPD2121	Clinical (unspecified phase)
0.7682	Intermediate Similarity	NPD5801	Clinical (unspecified phase)
0.768	Intermediate Similarity	NPD7393	Clinical (unspecified phase)
0.7652	Intermediate Similarity	NPD6531	Approved
0.7652	Intermediate Similarity	NPD6530	Approved
0.7647	Intermediate Similarity	NPD4795	Phase 2
0.7597	Intermediate Similarity	NPD7994	Phase 2
0.7592	Intermediate Similarity	NPD4926	Clinical (unspecified phase)
0.7577	Intermediate Similarity	NPD5417	Clinical (unspecified phase)
0.7571	Intermediate Similarity	NPD8091	Phase 3
0.7545	Intermediate Similarity	NPD1739	Approved
0.7545	Intermediate Similarity	NPD1740	Approved
0.7542	Intermediate Similarity	NPD4885	Approved
0.7541	Intermediate Similarity	NPD6525	Clinical (unspecified phase)
0.7532	Intermediate Similarity	NPD4952	Phase 3
0.7522	Intermediate Similarity	NPD6567	Clinical (unspecified phase)
0.7512	Intermediate Similarity	NPD1304	Clinical (unspecified phase)
0.7512	Intermediate Similarity	NPD1038	Approved
0.7511	Intermediate Similarity	NPD7823	Clinical (unspecified phase)
0.7511	Intermediate Similarity	NPD5040	Clinical (unspecified phase)
0.7511	Intermediate Similarity	NPD7558	Phase 2
0.7478	Intermediate Similarity	NPD8405	Clinical (unspecified phase)
0.7458	Intermediate Similarity	NPD5022	Discontinued
0.744	Intermediate Similarity	NPD6228	Discontinued
0.7437	Intermediate Similarity	NPD6741	Clinical (unspecified phase)
0.7437	Intermediate Similarity	NPD4373	Phase 2
0.7424	Intermediate Similarity	NPD5293	Phase 2
0.7391	Intermediate Similarity	NPD2412	Clinical (unspecified phase)
0.7383	Intermediate Similarity	NPD5509	Phase 1
0.7379	Intermediate Similarity	NPD2311	Clinical (unspecified phase)
0.7375	Intermediate Similarity	NPD7853	Phase 2
0.7353	Intermediate Similarity	NPD6962	Phase 2
0.735	Intermediate Similarity	NPD6824	Clinical (unspecified phase)
0.7331	Intermediate Similarity	NPD7426	Phase 1
0.7331	Intermediate Similarity	NPD7603	Discontinued
0.7319	Intermediate Similarity	NPD8279	Clinical (unspecified phase)
0.73	Intermediate Similarity	NPD4845	Discontinued
0.7297	Intermediate Similarity	NPD4987	Clinical (unspecified phase)
0.7292	Intermediate Similarity	NPD4850	Phase 1
0.7277	Intermediate Similarity	NPD6160	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD4368	Phase 2
0.7269	Intermediate Similarity	NPD1392	Approved
0.7269	Intermediate Similarity	NPD7198	Clinical (unspecified phase)
0.7269	Intermediate Similarity	NPD5559	Phase 2
0.7266	Intermediate Similarity	NPD7925	Phase 2
0.7266	Intermediate Similarity	NPD7924	Phase 2
0.7265	Intermediate Similarity	NPD3825	Phase 3
0.7257	Intermediate Similarity	NPD3947	Discontinued
0.7257	Intermediate Similarity	NPD5901	Discontinued
0.7255	Intermediate Similarity	NPD8284	Discontinued
0.7252	Intermediate Similarity	NPD7948	Phase 1
0.7241	Intermediate Similarity	NPD5612	Discontinued
0.7225	Intermediate Similarity	NPD3003	Approved
0.7225	Intermediate Similarity	NPD8403	Phase 1
0.7217	Intermediate Similarity	NPD7470	Discontinued
0.7217	Intermediate Similarity	NPD5475	Discontinued
0.7217	Intermediate Similarity	NPD5416	Discontinued
0.721	Intermediate Similarity	NPD3326	Clinical (unspecified phase)
0.7191	Intermediate Similarity	NPD1996	Discontinued
0.719	Intermediate Similarity	NPD6964	Approved
0.719	Intermediate Similarity	NPD6963	Approved
0.719	Intermediate Similarity	NPD2951	Discontinued
0.7188	Intermediate Similarity	NPD4118	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD7803	Approved
0.7183	Intermediate Similarity	NPD8049	Phase 2
0.7181	Intermediate Similarity	NPD5426	Phase 3
0.7181	Intermediate Similarity	NPD7689	Approved
0.7177	Intermediate Similarity	NPD8358	Approved
0.7173	Intermediate Similarity	NPD7547	Clinical (unspecified phase)
0.7169	Intermediate Similarity	NPD7690	Clinical (unspecified phase)
0.7165	Intermediate Similarity	NPD5867	Clinical (unspecified phase)
0.7162	Intermediate Similarity	NPD3324	Clinical (unspecified phase)
0.7156	Intermediate Similarity	NPD484	Approved
0.7149	Intermediate Similarity	NPD6172	Clinical (unspecified phase)
0.7149	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD5066	Phase 2
0.7143	Intermediate Similarity	NPD5067	Phase 2
0.7137	Intermediate Similarity	NPD5488	Discontinued
0.7126	Intermediate Similarity	NPD7955	Approved
0.7126	Intermediate Similarity	NPD7956	Approved
0.7126	Intermediate Similarity	NPD5802	Phase 2
0.7124	Intermediate Similarity	NPD6140	Clinical (unspecified phase)
0.7124	Intermediate Similarity	NPD5903	Approved
0.7124	Intermediate Similarity	NPD5902	Approved
0.7117	Intermediate Similarity	NPD802	Phase 2
0.7112	Intermediate Similarity	NPD7069	Discontinued
0.7101	Intermediate Similarity	NPD6306	Phase 2
0.7098	Intermediate Similarity	NPD5116	Phase 1
0.7095	Intermediate Similarity	NPD6968	Phase 2
0.7095	Intermediate Similarity	NPD6969	Phase 2
0.7095	Intermediate Similarity	NPD1659	Phase 1
0.7087	Intermediate Similarity	NPD2189	Approved
0.7087	Intermediate Similarity	NPD2187	Approved
0.7083	Intermediate Similarity	NPD7268	Clinical (unspecified phase)
0.7082	Intermediate Similarity	NPD3945	Discontinued
0.7076	Intermediate Similarity	NPD7194	Discontinued
0.7074	Intermediate Similarity	NPD2008	Discontinued
0.7072	Intermediate Similarity	NPD3921	Approved
0.7072	Intermediate Similarity	NPD3923	Approved
0.7072	Intermediate Similarity	NPD3922	Approved
0.7072	Intermediate Similarity	NPD3924	Approved
0.7047	Intermediate Similarity	NPD6961	Discontinued
0.7042	Intermediate Similarity	NPD8289	Discontinued
0.704	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD2411	Approved
0.7037	Intermediate Similarity	NPD8349	Phase 1
0.7035	Intermediate Similarity	NPD7000	Clinical (unspecified phase)
0.7035	Intermediate Similarity	NPD6999	Discontinued
0.7032	Intermediate Similarity	NPD4889	Approved
0.7031	Intermediate Similarity	NPD7708	Approved
0.7027	Intermediate Similarity	NPD4442	Phase 2
0.7025	Intermediate Similarity	NPD8512	Phase 3
0.7023	Intermediate Similarity	NPD5018	Phase 3
0.7016	Intermediate Similarity	NPD6473	Phase 1
0.7016	Intermediate Similarity	NPD3914	Clinical (unspecified phase)
0.7013	Intermediate Similarity	NPD7665	Phase 2
0.7013	Intermediate Similarity	NPD7666	Phase 3
0.7012	Intermediate Similarity	NPD4369	Phase 2
0.7009	Intermediate Similarity	NPD3794	Approved
0.7009	Intermediate Similarity	NPD3795	Approved
0.7004	Intermediate Similarity	NPD7404	Approved
0.7004	Intermediate Similarity	NPD1927	Discontinued
0.7	Intermediate Similarity	NPD5601	Phase 2
0.6992	Remote Similarity	NPD3801	Clinical (unspecified phase)
0.6988	Remote Similarity	NPD7068	Approved
0.6988	Remote Similarity	NPD7067	Approved
0.6988	Remote Similarity	NPD4440	Clinical (unspecified phase)
0.6987	Remote Similarity	NPD5513	Phase 2
0.6984	Remote Similarity	NPD6243	Phase 3
0.6984	Remote Similarity	NPD6244	Phase 3
0.6975	Remote Similarity	NPD5930	Phase 3
0.6972	Remote Similarity	NPD7414	Clinical (unspecified phase)
0.697	Remote Similarity	NPD6838	Clinical (unspecified phase)
0.6967	Remote Similarity	NPD3960	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD3816	Phase 1
0.6966	Remote Similarity	NPD3815	Phase 1
0.6962	Remote Similarity	NPD3354	Phase 2
0.696	Remote Similarity	NPD3962	Phase 2
0.696	Remote Similarity	NPD1768	Approved
0.696	Remote Similarity	NPD3959	Phase 2
0.696	Remote Similarity	NPD4548	Discontinued
0.6955	Remote Similarity	NPD7181	Phase 3
0.6947	Remote Similarity	NPD7408	Phase 2
0.6939	Remote Similarity	NPD6494	Phase 2
0.6935	Remote Similarity	NPD8016	Phase 3
0.6935	Remote Similarity	NPD8017	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD4418	Discontinued
0.6933	Remote Similarity	NPD6861	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD6770	Approved
0.6933	Remote Similarity	NPD3763	Approved
0.6932	Remote Similarity	NPD8100	Phase 3
0.6929	Remote Similarity	NPD6247	Clinical (unspecified phase)
0.6926	Remote Similarity	NPD3507	Phase 2
0.6926	Remote Similarity	NPD7001	Phase 3
0.692	Remote Similarity	NPD4376	Phase 3
0.692	Remote Similarity	NPD4372	Phase 1
0.692	Remote Similarity	NPD6569	Phase 2
0.692	Remote Similarity	NPD4989	Phase 2
0.6917	Remote Similarity	NPD6995	Phase 1
0.6913	Remote Similarity	NPD6176	Phase 1
0.6909	Remote Similarity	NPD8524	Approved
0.6908	Remote Similarity	NPD8363	Approved
0.6908	Remote Similarity	NPD7417	Discontinued
0.6908	Remote Similarity	NPD8364	Approved
0.6907	Remote Similarity	NPD3257	Approved
0.6903	Remote Similarity	NPD5512	Phase 3
0.6902	Remote Similarity	NPD1480	Clinical (unspecified phase)
0.6898	Remote Similarity	NPD6263	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD7222	Phase 2
0.6895	Remote Similarity	NPD7729	Clinical (unspecified phase)
0.6895	Remote Similarity	NPD4314	Approved
0.6895	Remote Similarity	NPD4313	Approved
0.6894	Remote Similarity	NPD5866	Approved
0.6891	Remote Similarity	NPD7395	Discontinued
0.6885	Remote Similarity	NPD5924	Discontinued
0.6883	Remote Similarity	NPD3397	Phase 2
0.688	Remote Similarity	NPD6716	Phase 1
0.6878	Remote Similarity	NPD2433	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD8246	Approved
0.6875	Remote Similarity	NPD8247	Approved
0.6875	Remote Similarity	NPD6180	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