NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	720.33
Volume:	734.386
LogP:	3.708
LogD:	3.433
LogS:	-3.604
# Rotatable Bonds:	8
TPSA:	178.8
# H-Bond Aceptor:	13
# H-Bond Donor:	5
# Rings:	6
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.182
Synthetic Accessibility Score:	4.854
Fsp3:	0.35
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.596
MDCK Permeability:	1.176184832729632e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.969
Human Intestinal Absorption (HIA):	0.077
20% Bioavailability (F20%):	0.84
30% Bioavailability (F30%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.023
Plasma Protein Binding (PPB):	95.53092193603516%
Volume Distribution (VD):	0.432
Pgp-substrate:	4.877126216888428%

ADMET: Metabolism

CYP1A2-inhibitor:	0.013
CYP1A2-substrate:	0.021
CYP2C19-inhibitor:	0.372
CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.885
CYP2C9-substrate:	0.086
CYP2D6-inhibitor:	0.075
CYP2D6-substrate:	0.151
CYP3A4-inhibitor:	0.968
CYP3A4-substrate:	0.151

ADMET: Excretion

Clearance (CL):	2.73
Half-life (T1/2):	0.683

ADMET: Toxicity

hERG Blockers:	0.09
Human Hepatotoxicity (H-HT):	0.926
Drug-inuced Liver Injury (DILI):	0.95
AMES Toxicity:	0.021
Rat Oral Acute Toxicity:	0.873
Maximum Recommended Daily Dose:	0.914
Skin Sensitization:	0.06
Carcinogencity:	0.067
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.039

Download Data

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

Natural Product: NPC478157

Natural Product ID:	NPC478157
*Common Name:**	benzylcarbonyl-Thr(1)-D-Phe-D-Ala-Pro-Trp-(1)
IUPAC Name:	N-[(3R,6R,9S,10R,13S,16S)-6-benzyl-13-(1H-indol-3-ylmethyl)-3,10-dimethyl-2,5,8,12,15-pentaoxo-11-oxa-1,4,7,14-tetrazabicyclo[14.3.0]nonadecan-9-yl]-2-phenylacetamide
Synonyms:
Standard InCHIKey:	YZLRYEXQPAXUDX-WRECJYPKSA-N
Standard InCHI:	InChI=1S/C40H44N6O7/c1-24-39(51)46-19-11-18-33(46)37(49)44-32(22-28-23-41-30-17-10-9-16-29(28)30)40(52)53-25(2)35(45-34(47)21-27-14-7-4-8-15-27)38(50)43-31(36(48)42-24)20-26-12-5-3-6-13-26/h3-10,12-17,23-25,31-33,35,41H,11,18-22H2,1-2H3,(H,42,48)(H,43,50)(H,44,49)(H,45,47)/t24-,25-,31-,32+,33+,35+/m1/s1
SMILES:	C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)O1)CC3=CNC4=CC=CC=C43)C)CC5=CC=CC=C5)NC(=O)CC6=CC=CC=C6
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	86302630
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO33637	Xenorhabdus sp. PB61.4	Species	Morganellaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24673206]

☑ 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	4
Others	1

Activity Type	# Activity
Cell Line	1
Organism	3
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT839	Cell Line	L6	Rattus norvegicus	IC50	=	92250	nM	PMID[24673206]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	5110	nM	PMID[24673206]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	56400	nM	PMID[24673206]
NPT2258	Organism	Plasmodium falciparum NF54	Plasmodium falciparum NF54	IC50	=	610	nM	PMID[24673206]
NPT2	Others	Unspecified		Ratio IC50	>	151	n.a.	PMID[24673206]

☑ 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 NPC478157 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	281
0.1-0.2	1487
0.2-0.3	10272
0.3-0.4	21509
0.4-0.5	3829
0.5-0.6	2595
0.6-0.7	1918
0.7-0.8	683
0.8-0.85	98
0.85-0.9	17
0.9-0.95	6
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9737	High Similarity	NPC478158
0.9188	High Similarity	NPC75634
0.915	High Similarity	NPC281049
0.9141	High Similarity	NPC54744
0.9119	High Similarity	NPC193761
0.9036	High Similarity	NPC162860
0.8934	High Similarity	NPC54420
0.8827	High Similarity	NPC476874
0.8737	High Similarity	NPC473376
0.8691	High Similarity	NPC321708
0.8691	High Similarity	NPC213629
0.868	High Similarity	NPC475506
0.866	High Similarity	NPC24370
0.866	High Similarity	NPC319232
0.8636	High Similarity	NPC155143
0.8622	High Similarity	NPC171317
0.8579	High Similarity	NPC293917
0.8545	High Similarity	NPC89987
0.8542	High Similarity	NPC17059
0.8528	High Similarity	NPC473640
0.8519	High Similarity	NPC478029
0.8505	High Similarity	NPC323752
0.8502	High Similarity	NPC477714
0.849	Intermediate Similarity	NPC94752
0.8485	Intermediate Similarity	NPC100321
0.848	Intermediate Similarity	NPC320968
0.8476	Intermediate Similarity	NPC64216
0.8473	Intermediate Similarity	NPC107077
0.8473	Intermediate Similarity	NPC223791
0.8454	Intermediate Similarity	NPC477715
0.8439	Intermediate Similarity	NPC110602
0.8439	Intermediate Similarity	NPC31385
0.8439	Intermediate Similarity	NPC75726
0.8426	Intermediate Similarity	NPC478028
0.8394	Intermediate Similarity	NPC235684
0.8364	Intermediate Similarity	NPC326363
0.8318	Intermediate Similarity	NPC191382
0.8318	Intermediate Similarity	NPC56109
0.8311	Intermediate Similarity	NPC314882
0.829	Intermediate Similarity	NPC228835
0.8284	Intermediate Similarity	NPC323927
0.8272	Intermediate Similarity	NPC283219
0.8272	Intermediate Similarity	NPC126709
0.8272	Intermediate Similarity	NPC248041
0.8263	Intermediate Similarity	NPC267885
0.8246	Intermediate Similarity	NPC478006
0.8223	Intermediate Similarity	NPC473763
0.8223	Intermediate Similarity	NPC117244
0.822	Intermediate Similarity	NPC145885
0.822	Intermediate Similarity	NPC14113
0.822	Intermediate Similarity	NPC84827
0.8219	Intermediate Similarity	NPC28945
0.8219	Intermediate Similarity	NPC285343
0.8211	Intermediate Similarity	NPC203468
0.8211	Intermediate Similarity	NPC110500
0.8211	Intermediate Similarity	NPC149155
0.8211	Intermediate Similarity	NPC325976
0.8177	Intermediate Similarity	NPC11126
0.8169	Intermediate Similarity	NPC155444
0.8157	Intermediate Similarity	NPC474877
0.8157	Intermediate Similarity	NPC475969
0.8157	Intermediate Similarity	NPC475859
0.8135	Intermediate Similarity	NPC91179
0.8134	Intermediate Similarity	NPC229348
0.8111	Intermediate Similarity	NPC470730
0.8111	Intermediate Similarity	NPC477176
0.8111	Intermediate Similarity	NPC470729
0.8111	Intermediate Similarity	NPC477175
0.8109	Intermediate Similarity	NPC227582
0.8082	Intermediate Similarity	NPC220852
0.8082	Intermediate Similarity	NPC63279
0.8079	Intermediate Similarity	NPC252338
0.8073	Intermediate Similarity	NPC477177
0.8061	Intermediate Similarity	NPC15102
0.8045	Intermediate Similarity	NPC297642
0.8037	Intermediate Similarity	NPC165743
0.8031	Intermediate Similarity	NPC59269
0.803	Intermediate Similarity	NPC74413
0.802	Intermediate Similarity	NPC315555
0.8009	Intermediate Similarity	NPC313640
0.8009	Intermediate Similarity	NPC125597
0.8	Intermediate Similarity	NPC478010
0.8	Intermediate Similarity	NPC478009
0.8	Intermediate Similarity	NPC78020
0.799	Intermediate Similarity	NPC470497
0.7982	Intermediate Similarity	NPC33949
0.798	Intermediate Similarity	NPC470499
0.7972	Intermediate Similarity	NPC36405
0.797	Intermediate Similarity	NPC99939
0.797	Intermediate Similarity	NPC308931
0.7952	Intermediate Similarity	NPC82370
0.7951	Intermediate Similarity	NPC300183
0.7949	Intermediate Similarity	NPC469896
0.7945	Intermediate Similarity	NPC322135
0.7936	Intermediate Similarity	NPC304307
0.7936	Intermediate Similarity	NPC118559
0.7936	Intermediate Similarity	NPC476491
0.7936	Intermediate Similarity	NPC124920
0.7936	Intermediate Similarity	NPC34580
0.7927	Intermediate Similarity	NPC469938
0.7921	Intermediate Similarity	NPC294693
0.7919	Intermediate Similarity	NPC165495
0.7915	Intermediate Similarity	NPC314056
0.7915	Intermediate Similarity	NPC153980
0.7915	Intermediate Similarity	NPC6865
0.7913	Intermediate Similarity	NPC260900
0.7908	Intermediate Similarity	NPC71037
0.79	Intermediate Similarity	NPC100547
0.7897	Intermediate Similarity	NPC213468
0.7897	Intermediate Similarity	NPC219336
0.7895	Intermediate Similarity	NPC314957
0.7892	Intermediate Similarity	NPC67288
0.7892	Intermediate Similarity	NPC131887
0.7887	Intermediate Similarity	NPC471192
0.7885	Intermediate Similarity	NPC277350
0.7881	Intermediate Similarity	NPC315467
0.787	Intermediate Similarity	NPC473317
0.7867	Intermediate Similarity	NPC72956
0.7864	Intermediate Similarity	NPC95240
0.7864	Intermediate Similarity	NPC223409
0.7861	Intermediate Similarity	NPC243716
0.7854	Intermediate Similarity	NPC261251
0.7853	Intermediate Similarity	NPC160105
0.785	Intermediate Similarity	NPC175474
0.7846	Intermediate Similarity	NPC217372
0.7846	Intermediate Similarity	NPC15573
0.7846	Intermediate Similarity	NPC183662
0.7846	Intermediate Similarity	NPC111275
0.7843	Intermediate Similarity	NPC262898
0.7842	Intermediate Similarity	NPC311276
0.7838	Intermediate Similarity	NPC323198
0.783	Intermediate Similarity	NPC471194
0.783	Intermediate Similarity	NPC471193
0.783	Intermediate Similarity	NPC207020
0.7828	Intermediate Similarity	NPC14288
0.7826	Intermediate Similarity	NPC476073
0.7816	Intermediate Similarity	NPC313985
0.7816	Intermediate Similarity	NPC195461
0.7816	Intermediate Similarity	NPC81654
0.7816	Intermediate Similarity	NPC49196
0.7816	Intermediate Similarity	NPC79129
0.7816	Intermediate Similarity	NPC249150
0.7815	Intermediate Similarity	NPC478013
0.7812	Intermediate Similarity	NPC63751
0.7808	Intermediate Similarity	NPC214142
0.7806	Intermediate Similarity	NPC55772
0.7798	Intermediate Similarity	NPC229893
0.7794	Intermediate Similarity	NPC179701
0.7793	Intermediate Similarity	NPC54803
0.7793	Intermediate Similarity	NPC321592
0.7793	Intermediate Similarity	NPC63031
0.7792	Intermediate Similarity	NPC153400
0.7784	Intermediate Similarity	NPC314603
0.7778	Intermediate Similarity	NPC469358
0.7767	Intermediate Similarity	NPC472285
0.7763	Intermediate Similarity	NPC474196
0.7758	Intermediate Similarity	NPC284888
0.7757	Intermediate Similarity	NPC474412
0.775	Intermediate Similarity	NPC62749
0.7729	Intermediate Similarity	NPC214428
0.7727	Intermediate Similarity	NPC472762
0.7723	Intermediate Similarity	NPC33064
0.7723	Intermediate Similarity	NPC245055
0.7721	Intermediate Similarity	NPC470732
0.7721	Intermediate Similarity	NPC470731
0.7718	Intermediate Similarity	NPC50503
0.7689	Intermediate Similarity	NPC125181
0.7689	Intermediate Similarity	NPC242872
0.7689	Intermediate Similarity	NPC263117
0.7686	Intermediate Similarity	NPC478012
0.7686	Intermediate Similarity	NPC478011
0.7679	Intermediate Similarity	NPC70155
0.7674	Intermediate Similarity	NPC477979
0.7668	Intermediate Similarity	NPC474561
0.7668	Intermediate Similarity	NPC49954
0.7668	Intermediate Similarity	NPC54988
0.7664	Intermediate Similarity	NPC118940
0.7661	Intermediate Similarity	NPC474195
0.7655	Intermediate Similarity	NPC184225
0.7655	Intermediate Similarity	NPC15801
0.7654	Intermediate Similarity	NPC314176
0.765	Intermediate Similarity	NPC475736
0.7644	Intermediate Similarity	NPC315491
0.7644	Intermediate Similarity	NPC45459
0.7635	Intermediate Similarity	NPC95783
0.7633	Intermediate Similarity	NPC52557
0.7626	Intermediate Similarity	NPC474896
0.7623	Intermediate Similarity	NPC69843
0.7621	Intermediate Similarity	NPC82472
0.7619	Intermediate Similarity	NPC317701
0.7613	Intermediate Similarity	NPC321939
0.7606	Intermediate Similarity	NPC469743
0.7604	Intermediate Similarity	NPC282231
0.7602	Intermediate Similarity	NPC235885
0.7602	Intermediate Similarity	NPC161861
0.7598	Intermediate Similarity	NPC476460
0.7594	Intermediate Similarity	NPC477065
0.7591	Intermediate Similarity	NPC31097
0.7581	Intermediate Similarity	NPC475778
0.758	Intermediate Similarity	NPC272174

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 NPC478157 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	163
0.1-0.2	461
0.2-0.3	745
0.3-0.4	1654
0.4-0.5	2434
0.5-0.6	2448
0.6-0.7	1053
0.7-0.8	156
0.8-0.85	32
0.85-0.9	4
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8945	High Similarity	NPD7470	Discontinued
0.8756	High Similarity	NPD7944	Discontinued
0.8744	High Similarity	NPD8493	Clinical (unspecified phase)
0.8663	High Similarity	NPD8013	Clinical (unspecified phase)
0.8614	High Similarity	NPD7998	Clinical (unspecified phase)
0.8579	High Similarity	NPD7621	Clinical (unspecified phase)
0.8502	High Similarity	NPD8405	Clinical (unspecified phase)
0.8454	Intermediate Similarity	NPD8406	Clinical (unspecified phase)
0.8431	Intermediate Similarity	NPD7809	Clinical (unspecified phase)
0.8333	Intermediate Similarity	NPD7951	Approved
0.8333	Intermediate Similarity	NPD7790	Approved
0.8333	Intermediate Similarity	NPD7952	Approved
0.8333	Intermediate Similarity	NPD7950	Approved
0.8333	Intermediate Similarity	NPD7953	Approved
0.8333	Intermediate Similarity	NPD7789	Approved
0.8333	Intermediate Similarity	NPD7791	Approved
0.8325	Intermediate Similarity	NPD7958	Clinical (unspecified phase)
0.8325	Intermediate Similarity	NPD7957	Phase 1
0.8318	Intermediate Similarity	NPD7781	Approved
0.8318	Intermediate Similarity	NPD7780	Approved
0.8261	Intermediate Similarity	NPD7594	Clinical (unspecified phase)
0.8238	Intermediate Similarity	NPD2092	Phase 2
0.8238	Intermediate Similarity	NPD2094	Phase 2
0.8238	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.8238	Intermediate Similarity	NPD2095	Phase 2
0.8235	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.8218	Intermediate Similarity	NPD7903	Clinical (unspecified phase)
0.8211	Intermediate Similarity	NPD482	Approved
0.8196	Intermediate Similarity	NPD2091	Phase 2
0.8196	Intermediate Similarity	NPD2096	Phase 2
0.8186	Intermediate Similarity	NPD7730	Approved
0.8186	Intermediate Similarity	NPD7731	Approved
0.8182	Intermediate Similarity	NPD7971	Clinical (unspecified phase)
0.8182	Intermediate Similarity	NPD7970	Approved
0.8182	Intermediate Similarity	NPD8112	Clinical (unspecified phase)
0.8168	Intermediate Similarity	NPD749	Clinical (unspecified phase)
0.8111	Intermediate Similarity	NPD7824	Approved
0.81	Intermediate Similarity	NPD7618	Phase 3
0.81	Intermediate Similarity	NPD7619	Phase 3
0.8098	Intermediate Similarity	NPD8272	Phase 2
0.8093	Intermediate Similarity	NPD7271	Approved
0.8086	Intermediate Similarity	NPD8093	Discontinued
0.8068	Intermediate Similarity	NPD7947	Clinical (unspecified phase)
0.8063	Intermediate Similarity	NPD750	Phase 2
0.8058	Intermediate Similarity	NPD7001	Phase 3
0.8041	Intermediate Similarity	NPD6595	Phase 3
0.8019	Intermediate Similarity	NPD6838	Clinical (unspecified phase)
0.8019	Intermediate Similarity	NPD8322	Phase 2
0.801	Intermediate Similarity	NPD5426	Phase 3
0.799	Intermediate Similarity	NPD7825	Clinical (unspecified phase)
0.7972	Intermediate Similarity	NPD7711	Discontinued
0.7972	Intermediate Similarity	NPD7603	Discontinued
0.7961	Intermediate Similarity	NPD8072	Approved
0.7934	Intermediate Similarity	NPD8000	Clinical (unspecified phase)
0.7913	Intermediate Similarity	NPD8073	Approved
0.7889	Intermediate Similarity	NPD8431	Approved
0.7879	Intermediate Similarity	NPD6610	Clinical (unspecified phase)
0.7846	Intermediate Similarity	NPD6203	Clinical (unspecified phase)
0.7816	Intermediate Similarity	NPD4600	Approved
0.7816	Intermediate Similarity	NPD4601	Approved
0.7793	Intermediate Similarity	NPD8094	Discontinued
0.7756	Intermediate Similarity	NPD7948	Phase 1
0.7751	Intermediate Similarity	NPD5901	Discontinued
0.7751	Intermediate Similarity	NPD7712	Clinical (unspecified phase)
0.7748	Intermediate Similarity	NPD7688	Phase 1
0.7725	Intermediate Similarity	NPD2509	Approved
0.7725	Intermediate Similarity	NPD2510	Approved
0.7714	Intermediate Similarity	NPD6732	Clinical (unspecified phase)
0.7711	Intermediate Similarity	NPD6141	Clinical (unspecified phase)
0.768	Intermediate Similarity	NPD4184	Clinical (unspecified phase)
0.7677	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.7673	Intermediate Similarity	NPD8110	Clinical (unspecified phase)
0.767	Intermediate Similarity	NPD5003	Discontinued
0.7656	Intermediate Similarity	NPD5721	Clinical (unspecified phase)
0.7647	Intermediate Similarity	NPD8289	Discontinued
0.7644	Intermediate Similarity	NPD484	Approved
0.7642	Intermediate Similarity	NPD7666	Phase 3
0.7642	Intermediate Similarity	NPD7665	Phase 2
0.7621	Intermediate Similarity	NPD6449	Clinical (unspecified phase)
0.7621	Intermediate Similarity	NPD7818	Clinical (unspecified phase)
0.7604	Intermediate Similarity	NPD7823	Clinical (unspecified phase)
0.7596	Intermediate Similarity	NPD7000	Clinical (unspecified phase)
0.7596	Intermediate Similarity	NPD6999	Discontinued
0.7596	Intermediate Similarity	NPD6661	Clinical (unspecified phase)
0.7591	Intermediate Similarity	NPD8356	Approved
0.7583	Intermediate Similarity	NPD8114	Approved
0.7583	Intermediate Similarity	NPD8115	Approved
0.7576	Intermediate Similarity	NPD2144	Approved
0.7561	Intermediate Similarity	NPD6665	Discontinued
0.7555	Intermediate Similarity	NPD7576	Discontinued
0.7536	Intermediate Similarity	NPD6176	Phase 1
0.7536	Intermediate Similarity	NPD2121	Clinical (unspecified phase)
0.7534	Intermediate Similarity	NPD8430	Approved
0.7524	Intermediate Similarity	NPD7727	Phase 2
0.7523	Intermediate Similarity	NPD8271	Discontinued
0.7511	Intermediate Similarity	NPD8372	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD8458	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD6664	Approved
0.7477	Intermediate Similarity	NPD7716	Approved
0.7477	Intermediate Similarity	NPD7717	Approved
0.7476	Intermediate Similarity	NPD8248	Clinical (unspecified phase)
0.7475	Intermediate Similarity	NPD5065	Approved
0.7465	Intermediate Similarity	NPD8488	Clinical (unspecified phase)
0.7464	Intermediate Similarity	NPD7777	Approved
0.7464	Intermediate Similarity	NPD7778	Approved
0.7464	Intermediate Similarity	NPD53	Approved
0.7463	Intermediate Similarity	NPD3038	Discontinued
0.7463	Intermediate Similarity	NPD4499	Approved
0.7451	Intermediate Similarity	NPD3961	Discontinued
0.7443	Intermediate Similarity	NPD5818	Discontinued
0.7441	Intermediate Similarity	NPD7817	Phase 1
0.7432	Intermediate Similarity	NPD6995	Phase 1
0.7427	Intermediate Similarity	NPD6180	Clinical (unspecified phase)
0.7415	Intermediate Similarity	NPD7233	Approved
0.7415	Intermediate Similarity	NPD7234	Approved
0.7409	Intermediate Similarity	NPD6578	Clinical (unspecified phase)
0.7401	Intermediate Similarity	NPD8119	Discontinued
0.7398	Intermediate Similarity	NPD4174	Clinical (unspecified phase)
0.7397	Intermediate Similarity	NPD3389	Approved
0.7397	Intermediate Similarity	NPD3393	Approved
0.7397	Intermediate Similarity	NPD3394	Approved
0.7387	Intermediate Similarity	NPD6615	Clinical (unspecified phase)
0.7378	Intermediate Similarity	NPD6164	Phase 2
0.7378	Intermediate Similarity	NPD6165	Phase 2
0.7366	Intermediate Similarity	NPD8103	Clinical (unspecified phase)
0.7363	Intermediate Similarity	NPD4076	Approved
0.7363	Intermediate Similarity	NPD4079	Approved
0.7354	Intermediate Similarity	NPD6824	Clinical (unspecified phase)
0.7336	Intermediate Similarity	NPD3947	Discontinued
0.733	Intermediate Similarity	NPD7878	Phase 2
0.7321	Intermediate Similarity	NPD4602	Approved
0.7313	Intermediate Similarity	NPD3505	Approved
0.7313	Intermediate Similarity	NPD3506	Approved
0.7311	Intermediate Similarity	NPD4501	Approved
0.7311	Intermediate Similarity	NPD4500	Approved
0.7308	Intermediate Similarity	NPD5483	Clinical (unspecified phase)
0.7306	Intermediate Similarity	NPD276	Clinical (unspecified phase)
0.73	Intermediate Similarity	NPD5322	Clinical (unspecified phase)
0.7295	Intermediate Similarity	NPD2564	Approved
0.7295	Intermediate Similarity	NPD2565	Phase 2
0.7282	Intermediate Similarity	NPD3486	Clinical (unspecified phase)
0.7277	Intermediate Similarity	NPD5017	Discontinued
0.7273	Intermediate Similarity	NPD5069	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD2844	Phase 3
0.7269	Intermediate Similarity	NPD5559	Phase 2
0.7264	Intermediate Similarity	NPD4075	Phase 2
0.7256	Intermediate Similarity	NPD6987	Phase 1
0.7249	Intermediate Similarity	NPD6263	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD6965	Clinical (unspecified phase)
0.7241	Intermediate Similarity	NPD6452	Discontinued
0.7233	Intermediate Similarity	NPD6217	Discontinued
0.7233	Intermediate Similarity	NPD4426	Clinical (unspecified phase)
0.723	Intermediate Similarity	NPD6479	Discontinued
0.722	Intermediate Similarity	NPD6178	Phase 3
0.722	Intermediate Similarity	NPD7564	Discontinued
0.7217	Intermediate Similarity	NPD5040	Clinical (unspecified phase)
0.721	Intermediate Similarity	NPD2921	Clinical (unspecified phase)
0.7209	Intermediate Similarity	NPD5487	Phase 1
0.7207	Intermediate Similarity	NPD8256	Approved
0.7207	Intermediate Similarity	NPD8258	Clinical (unspecified phase)
0.7207	Intermediate Similarity	NPD8257	Approved
0.7206	Intermediate Similarity	NPD3178	Discontinued
0.7202	Intermediate Similarity	NPD2125	Clinical (unspecified phase)
0.719	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7185	Intermediate Similarity	NPD5482	Discontinued
0.7183	Intermediate Similarity	NPD6249	Phase 2
0.7183	Intermediate Similarity	NPD6248	Phase 2
0.7182	Intermediate Similarity	NPD4852	Phase 2
0.7177	Intermediate Similarity	NPD6630	Clinical (unspecified phase)
0.7176	Intermediate Similarity	NPD8169	Discontinued
0.7168	Intermediate Similarity	NPD6173	Approved
0.7163	Intermediate Similarity	NPD4334	Discontinued
0.7162	Intermediate Similarity	NPD8374	Phase 3
0.7161	Intermediate Similarity	NPD7921	Approved
0.7157	Intermediate Similarity	NPD5897	Approved
0.7157	Intermediate Similarity	NPD5899	Approved
0.7157	Intermediate Similarity	NPD5898	Approved
0.7143	Intermediate Similarity	NPD8122	Approved
0.7143	Intermediate Similarity	NPD7865	Approved
0.7143	Intermediate Similarity	NPD8123	Approved
0.7137	Intermediate Similarity	NPD8247	Approved
0.7137	Intermediate Similarity	NPD8246	Approved
0.7136	Intermediate Similarity	NPD7946	Pre-registration
0.7136	Intermediate Similarity	NPD4397	Phase 1
0.7136	Intermediate Similarity	NPD5475	Discontinued
0.7136	Intermediate Similarity	NPD3607	Clinical (unspecified phase)
0.7129	Intermediate Similarity	NPD8063	Discontinued
0.7112	Intermediate Similarity	NPD8329	Phase 3
0.711	Intermediate Similarity	NPD8410	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD7689	Approved
0.71	Intermediate Similarity	NPD4885	Approved
0.7097	Intermediate Similarity	NPD8098	Approved
0.7091	Intermediate Similarity	NPD4900	Clinical (unspecified phase)
0.7087	Intermediate Similarity	NPD5596	Phase 2
0.7085	Intermediate Similarity	NPD5612	Discontinued
0.7074	Intermediate Similarity	NPD6977	Clinical (unspecified phase)
0.7074	Intermediate Similarity	NPD6978	Phase 2
0.7072	Intermediate Similarity	NPD3794	Approved
0.7072	Intermediate Similarity	NPD3795	Approved
0.7069	Intermediate Similarity	NPD8047	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