NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	420.09
Volume:	361.308
LogP:	1.334
LogD:	0.604
LogS:	-3.16
# Rotatable Bonds:	7
TPSA:	135.89
# H-Bond Aceptor:	8
# H-Bond Donor:	7
# Rings:	3
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.233
Synthetic Accessibility Score:	3.429
Fsp3:	0.353
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.579
MDCK Permeability:	4.646441539080115e-06
Pgp-inhibitor:	0.0
Pgp-substrate:	0.945
Human Intestinal Absorption (HIA):	0.333
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.619

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.464
Plasma Protein Binding (PPB):	62.53016662597656%
Volume Distribution (VD):	0.702
Pgp-substrate:	47.06039047241211%

ADMET: Metabolism

CYP1A2-inhibitor:	0.047
CYP1A2-substrate:	0.199
CYP2C19-inhibitor:	0.183
CYP2C19-substrate:	0.055
CYP2C9-inhibitor:	0.077
CYP2C9-substrate:	0.107
CYP2D6-inhibitor:	0.273
CYP2D6-substrate:	0.515
CYP3A4-inhibitor:	0.056
CYP3A4-substrate:	0.06

ADMET: Excretion

Clearance (CL):	3.09
Half-life (T1/2):	0.659

ADMET: Toxicity

hERG Blockers:	0.25
Human Hepatotoxicity (H-HT):	0.073
Drug-inuced Liver Injury (DILI):	0.064
AMES Toxicity:	0.057
Rat Oral Acute Toxicity:	0.815
Maximum Recommended Daily Dose:	0.908
Skin Sensitization:	0.23
Carcinogencity:	0.218
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.139

Download Data

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

Natural Product: NPC477167

Natural Product ID:	NPC477167
*Common Name:**	8,9-Dihydrobarettin
IUPAC Name:	2-[3-[5-[(6-bromo-1H-indol-3-yl)methyl]-3,6-dioxopiperazin-2-yl]propyl]guanidine;2,2,2-trifluoroacetic acid
Synonyms:	8,9-dihydrobarettin
Standard InCHIKey:	YPQZHDIFCNYAMS-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C17H21BrN6O2.C2HF3O2/c18-10-3-4-11-9(8-22-13(11)7-10)6-14-16(26)23-12(15(25)24-14)2-1-5-21-17(19)20;3-2(4,5)1(6)7/h3-4,7-8,12,14,22H,1-2,5-6H2,(H,23,26)(H,24,25)(H4,19,20,21);(H,6,7)
SMILES:	C1=CC2=C(C=C1Br)NC=C2CC3C(=O)NC(C(=O)N3)CCCN=C(N)N.C(=O)(C(F)(F)F)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	49797534
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*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
NPO5772	Geodia barretti	Species	Geodiidae	Eukaryota	n.a.	collected at 50-60 m depth in the Kosterfjord on the Swedish west coast	2001-MAR	PMID[15043412]
NPO5772	Geodia barretti	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15043412]
NPO5772	Geodia barretti	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17067154]
NPO5772	Geodia barretti	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18271554]
NPO5772	Geodia barretti	Species	Geodiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26222779]
NPO5772	Geodia barretti	Species	Geodiidae	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
EC50	2
Others	1

Activity Type	# Activity
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT5137	Organism	Balanus improvisus	Balanus improvisus	EC50	=	7000	nM	PMID[15043412]
NPT5137	Organism	Balanus improvisus	Balanus improvisus	EC50	=	7900	nM	PMID[15043412]
NPT5137	Organism	Balanus improvisus	Balanus improvisus	LC50	=	4	ug/ml	PMID[15043412]

☑ 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 NPC477167 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	422
0.1-0.2	4494
0.2-0.3	24344
0.3-0.4	7344
0.4-0.5	2693
0.5-0.6	2157
0.6-0.7	974
0.7-0.8	253
0.8-0.85	12
0.85-0.9	0
0.9-0.95	2
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473342
0.9653	High Similarity	NPC477166
0.9653	High Similarity	NPC304187
0.8824	High Similarity	NPC17751
0.8663	High Similarity	NPC474561
0.8663	High Similarity	NPC49954
0.8656	High Similarity	NPC106771
0.8656	High Similarity	NPC303820
0.8656	High Similarity	NPC23420
0.8656	High Similarity	NPC205254
0.8647	High Similarity	NPC279918
0.8613	High Similarity	NPC63751
0.861	High Similarity	NPC52909
0.861	High Similarity	NPC94211
0.861	High Similarity	NPC475935
0.8596	High Similarity	NPC282231
0.8492	Intermediate Similarity	NPC307191
0.8469	Intermediate Similarity	NPC477114
0.8448	Intermediate Similarity	NPC54988
0.8448	Intermediate Similarity	NPC160105
0.8439	Intermediate Similarity	NPC194640
0.8427	Intermediate Similarity	NPC59269
0.8418	Intermediate Similarity	NPC280297
0.8391	Intermediate Similarity	NPC280864
0.8333	Intermediate Similarity	NPC247987
0.8297	Intermediate Similarity	NPC108011
0.8265	Intermediate Similarity	NPC128084
0.8258	Intermediate Similarity	NPC314603
0.8246	Intermediate Similarity	NPC141926
0.8222	Intermediate Similarity	NPC248454
0.815	Intermediate Similarity	NPC475736
0.814	Intermediate Similarity	NPC469786
0.814	Intermediate Similarity	NPC25008
0.814	Intermediate Similarity	NPC469765
0.814	Intermediate Similarity	NPC73952
0.814	Intermediate Similarity	NPC469760
0.814	Intermediate Similarity	NPC259644
0.814	Intermediate Similarity	NPC469763
0.8105	Intermediate Similarity	NPC262898
0.8103	Intermediate Similarity	NPC469762
0.8092	Intermediate Similarity	NPC75540
0.8092	Intermediate Similarity	NPC211572
0.8092	Intermediate Similarity	NPC70922
0.8092	Intermediate Similarity	NPC80597
0.8092	Intermediate Similarity	NPC212376
0.8081	Intermediate Similarity	NPC207020
0.8059	Intermediate Similarity	NPC143872
0.8056	Intermediate Similarity	NPC477611
0.8053	Intermediate Similarity	NPC179701
0.8046	Intermediate Similarity	NPC285469
0.8046	Intermediate Similarity	NPC469785
0.8043	Intermediate Similarity	NPC163055
0.8042	Intermediate Similarity	NPC188821
0.8042	Intermediate Similarity	NPC474180
0.7969	Intermediate Similarity	NPC474389
0.7967	Intermediate Similarity	NPC474958
0.7957	Intermediate Similarity	NPC15102
0.7956	Intermediate Similarity	NPC64055
0.7933	Intermediate Similarity	NPC109447
0.7931	Intermediate Similarity	NPC232798
0.7921	Intermediate Similarity	NPC311276
0.7912	Intermediate Similarity	NPC203468
0.7912	Intermediate Similarity	NPC110500
0.7912	Intermediate Similarity	NPC149155
0.7895	Intermediate Similarity	NPC314372
0.7892	Intermediate Similarity	NPC474195
0.7892	Intermediate Similarity	NPC233936
0.7877	Intermediate Similarity	NPC274229
0.7869	Intermediate Similarity	NPC267885
0.7865	Intermediate Similarity	NPC16667
0.7861	Intermediate Similarity	NPC2272
0.7861	Intermediate Similarity	NPC477610
0.7853	Intermediate Similarity	NPC230869
0.7853	Intermediate Similarity	NPC88315
0.7833	Intermediate Similarity	NPC49217
0.7831	Intermediate Similarity	NPC321708
0.7826	Intermediate Similarity	NPC474196
0.7821	Intermediate Similarity	NPC149265
0.7817	Intermediate Similarity	NPC473376
0.7807	Intermediate Similarity	NPC165495
0.7802	Intermediate Similarity	NPC82331
0.779	Intermediate Similarity	NPC78020
0.779	Intermediate Similarity	NPC201700
0.7784	Intermediate Similarity	NPC34844
0.7784	Intermediate Similarity	NPC207726
0.7784	Intermediate Similarity	NPC248041
0.7784	Intermediate Similarity	NPC233050
0.7784	Intermediate Similarity	NPC283219
0.7784	Intermediate Similarity	NPC126709
0.7784	Intermediate Similarity	NPC276540
0.7778	Intermediate Similarity	NPC190296
0.7772	Intermediate Similarity	NPC222018
0.7772	Intermediate Similarity	NPC121903
0.7765	Intermediate Similarity	NPC470203
0.776	Intermediate Similarity	NPC288074
0.775	Intermediate Similarity	NPC80596
0.7737	Intermediate Similarity	NPC213629
0.7731	Intermediate Similarity	NPC201831
0.7731	Intermediate Similarity	NPC17487
0.7725	Intermediate Similarity	NPC235684
0.7722	Intermediate Similarity	NPC40779
0.7714	Intermediate Similarity	NPC105818
0.7714	Intermediate Similarity	NPC24678
0.7714	Intermediate Similarity	NPC156003
0.7709	Intermediate Similarity	NPC470204
0.7709	Intermediate Similarity	NPC131718
0.7707	Intermediate Similarity	NPC477609
0.7701	Intermediate Similarity	NPC243381
0.7701	Intermediate Similarity	NPC275292
0.7696	Intermediate Similarity	NPC477107
0.7696	Intermediate Similarity	NPC477109
0.7696	Intermediate Similarity	NPC477108
0.7692	Intermediate Similarity	NPC471536
0.7688	Intermediate Similarity	NPC159856
0.7684	Intermediate Similarity	NPC317030
0.7684	Intermediate Similarity	NPC17059
0.768	Intermediate Similarity	NPC242209
0.7656	Intermediate Similarity	NPC243716
0.7654	Intermediate Similarity	NPC67056
0.7653	Intermediate Similarity	NPC474318
0.7653	Intermediate Similarity	NPC475914
0.7653	Intermediate Similarity	NPC268744
0.7653	Intermediate Similarity	NPC153123
0.7653	Intermediate Similarity	NPC201266
0.7653	Intermediate Similarity	NPC220797
0.765	Intermediate Similarity	NPC194411
0.765	Intermediate Similarity	NPC280548
0.7644	Intermediate Similarity	NPC316069
0.7634	Intermediate Similarity	NPC68354
0.7634	Intermediate Similarity	NPC145885
0.7634	Intermediate Similarity	NPC14113
0.7634	Intermediate Similarity	NPC84827
0.7632	Intermediate Similarity	NPC94752
0.7632	Intermediate Similarity	NPC474707
0.7619	Intermediate Similarity	NPC228835
0.7614	Intermediate Similarity	NPC269203
0.7614	Intermediate Similarity	NPC166209
0.7614	Intermediate Similarity	NPC77241
0.7614	Intermediate Similarity	NPC13456
0.7611	Intermediate Similarity	NPC122141
0.7594	Intermediate Similarity	NPC213468
0.7592	Intermediate Similarity	NPC204565
0.7588	Intermediate Similarity	NPC125746
0.7586	Intermediate Similarity	NPC204141
0.7586	Intermediate Similarity	NPC320968
0.7586	Intermediate Similarity	NPC72956
0.7579	Intermediate Similarity	NPC163421
0.7579	Intermediate Similarity	NPC188387
0.7558	Intermediate Similarity	NPC469768
0.7558	Intermediate Similarity	NPC469779
0.7558	Intermediate Similarity	NPC469784
0.7558	Intermediate Similarity	NPC469761
0.7558	Intermediate Similarity	NPC469780
0.7558	Intermediate Similarity	NPC469783
0.7558	Intermediate Similarity	NPC469767
0.7557	Intermediate Similarity	NPC37548
0.7556	Intermediate Similarity	NPC135141
0.7556	Intermediate Similarity	NPC92796
0.7552	Intermediate Similarity	NPC173028
0.7552	Intermediate Similarity	NPC65215
0.7549	Intermediate Similarity	NPC6865
0.7549	Intermediate Similarity	NPC153980
0.754	Intermediate Similarity	NPC151939
0.7538	Intermediate Similarity	NPC473761
0.7529	Intermediate Similarity	NPC96102
0.7527	Intermediate Similarity	NPC102423
0.7527	Intermediate Similarity	NPC275305
0.7527	Intermediate Similarity	NPC37423
0.7514	Intermediate Similarity	NPC469766
0.7514	Intermediate Similarity	NPC470498
0.7513	Intermediate Similarity	NPC95783
0.7513	Intermediate Similarity	NPC470499
0.7512	Intermediate Similarity	NPC54744
0.75	Intermediate Similarity	NPC11126
0.75	Intermediate Similarity	NPC471957
0.75	Intermediate Similarity	NPC73767
0.75	Intermediate Similarity	NPC55772
0.7486	Intermediate Similarity	NPC470508
0.7485	Intermediate Similarity	NPC84911
0.7485	Intermediate Similarity	NPC105127
0.7475	Intermediate Similarity	NPC477004
0.7463	Intermediate Similarity	NPC470505
0.7463	Intermediate Similarity	NPC471193
0.7463	Intermediate Similarity	NPC471194
0.746	Intermediate Similarity	NPC300688
0.7447	Intermediate Similarity	NPC111275
0.7444	Intermediate Similarity	NPC141353
0.7442	Intermediate Similarity	NPC63031
0.744	Intermediate Similarity	NPC471192
0.7437	Intermediate Similarity	NPC470497
0.7436	Intermediate Similarity	NPC99666
0.7435	Intermediate Similarity	NPC110158
0.7427	Intermediate Similarity	NPC29886
0.7427	Intermediate Similarity	NPC261195
0.7424	Intermediate Similarity	NPC473640
0.7424	Intermediate Similarity	NPC171317
0.7423	Intermediate Similarity	NPC231536
0.7421	Intermediate Similarity	NPC71037
0.7415	Intermediate Similarity	NPC54981
0.7407	Intermediate Similarity	NPC176199

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 NPC477167 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	203
0.1-0.2	634
0.2-0.3	1184
0.3-0.4	2192
0.4-0.5	2361
0.5-0.6	2014
0.6-0.7	504
0.7-0.8	58
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
0.8352	Intermediate Similarity	NPD4184	Clinical (unspecified phase)
0.8232	Intermediate Similarity	NPD6595	Phase 3
0.7978	Intermediate Similarity	NPD8386	Phase 2
0.7912	Intermediate Similarity	NPD482	Approved
0.7872	Intermediate Similarity	NPD8431	Approved
0.7861	Intermediate Similarity	NPD6610	Clinical (unspecified phase)
0.7849	Intermediate Similarity	NPD2092	Phase 2
0.7849	Intermediate Similarity	NPD2095	Phase 2
0.7849	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.7849	Intermediate Similarity	NPD2094	Phase 2
0.7831	Intermediate Similarity	NPD8110	Clinical (unspecified phase)
0.7828	Intermediate Similarity	NPD8493	Clinical (unspecified phase)
0.7814	Intermediate Similarity	NPD4128	Approved
0.7807	Intermediate Similarity	NPD2091	Phase 2
0.7807	Intermediate Similarity	NPD2096	Phase 2
0.7772	Intermediate Similarity	NPD749	Clinical (unspecified phase)
0.773	Intermediate Similarity	NPD6203	Clinical (unspecified phase)
0.7717	Intermediate Similarity	NPD5065	Approved
0.7688	Intermediate Similarity	NPD4076	Approved
0.7688	Intermediate Similarity	NPD4079	Approved
0.7667	Intermediate Similarity	NPD8026	Phase 1
0.7657	Intermediate Similarity	NPD4374	Clinical (unspecified phase)
0.7635	Intermediate Similarity	NPD8458	Clinical (unspecified phase)
0.7634	Intermediate Similarity	NPD3505	Approved
0.7634	Intermediate Similarity	NPD2144	Approved
0.7634	Intermediate Similarity	NPD3506	Approved
0.7624	Intermediate Similarity	NPD7809	Clinical (unspecified phase)
0.7602	Intermediate Similarity	NPD786	Approved
0.7598	Intermediate Similarity	NPD8488	Clinical (unspecified phase)
0.7568	Intermediate Similarity	NPD750	Phase 2
0.7557	Intermediate Similarity	NPD3100	Discontinued
0.7551	Intermediate Similarity	NPD7948	Phase 1
0.754	Intermediate Similarity	NPD4181	Approved
0.7539	Intermediate Similarity	NPD706	Phase 1
0.7529	Intermediate Similarity	NPD198	Clinical (unspecified phase)
0.7527	Intermediate Similarity	NPD2928	Phase 2
0.7514	Intermediate Similarity	NPD1722	Approved
0.7513	Intermediate Similarity	NPD3038	Discontinued
0.75	Intermediate Similarity	NPD5069	Clinical (unspecified phase)
0.7487	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7415	Intermediate Similarity	NPD8013	Clinical (unspecified phase)
0.7409	Intermediate Similarity	NPD3486	Clinical (unspecified phase)
0.7387	Intermediate Similarity	NPD7621	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.7366	Intermediate Similarity	NPD1325	Approved
0.7366	Intermediate Similarity	NPD1326	Approved
0.7363	Intermediate Similarity	NPD8073	Approved
0.7327	Intermediate Similarity	NPD8072	Approved
0.732	Intermediate Similarity	NPD3961	Discontinued
0.7308	Intermediate Similarity	NPD7970	Approved
0.7308	Intermediate Similarity	NPD8112	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD7971	Clinical (unspecified phase)
0.7295	Intermediate Similarity	NPD7594	Clinical (unspecified phase)
0.7263	Intermediate Similarity	NPD1183	Approved
0.7255	Intermediate Similarity	NPD7958	Clinical (unspecified phase)
0.7255	Intermediate Similarity	NPD7957	Phase 1
0.7243	Intermediate Similarity	NPD4890	Phase 2
0.7238	Intermediate Similarity	NPD8406	Clinical (unspecified phase)
0.7236	Intermediate Similarity	NPD7818	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD4463	Approved
0.7222	Intermediate Similarity	NPD4462	Approved
0.7222	Intermediate Similarity	NPD2172	Phase 1
0.722	Intermediate Similarity	NPD8410	Clinical (unspecified phase)
0.7219	Intermediate Similarity	NPD4640	Approved
0.7219	Intermediate Similarity	NPD4639	Approved
0.7219	Intermediate Similarity	NPD4638	Approved
0.7214	Intermediate Similarity	NPD3814	Phase 1
0.7211	Intermediate Similarity	NPD2367	Phase 2
0.7211	Intermediate Similarity	NPD6375	Clinical (unspecified phase)
0.7211	Intermediate Similarity	NPD4075	Phase 2
0.7206	Intermediate Similarity	NPD5901	Discontinued
0.7206	Intermediate Similarity	NPD8272	Phase 2
0.72	Intermediate Similarity	NPD2070	Approved
0.72	Intermediate Similarity	NPD2071	Approved
0.72	Intermediate Similarity	NPD2069	Approved
0.72	Intermediate Similarity	NPD2068	Approved
0.7196	Intermediate Similarity	NPD966	Clinical (unspecified phase)
0.7184	Intermediate Similarity	NPD2189	Approved
0.7184	Intermediate Similarity	NPD2187	Approved
0.7184	Intermediate Similarity	NPD7947	Clinical (unspecified phase)
0.7173	Intermediate Similarity	NPD1272	Clinical (unspecified phase)
0.7172	Intermediate Similarity	NPD4615	Phase 2
0.7143	Intermediate Similarity	NPD5934	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD2837	Discontinued
0.7136	Intermediate Similarity	NPD1304	Clinical (unspecified phase)
0.7136	Intermediate Similarity	NPD1038	Approved
0.7115	Intermediate Similarity	NPD7825	Clinical (unspecified phase)
0.7115	Intermediate Similarity	NPD3013	Phase 3
0.7115	Intermediate Similarity	NPD3014	Clinical (unspecified phase)
0.7114	Intermediate Similarity	NPD6664	Approved
0.7111	Intermediate Similarity	NPD4702	Approved
0.7111	Intermediate Similarity	NPD4703	Approved
0.7094	Intermediate Similarity	NPD484	Approved
0.7087	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.7085	Intermediate Similarity	NPD3404	Approved
0.7081	Intermediate Similarity	NPD7470	Discontinued
0.7074	Intermediate Similarity	NPD5611	Phase 2
0.7071	Intermediate Similarity	NPD5117	Phase 2
0.7062	Intermediate Similarity	NPD1895	Discontinued
0.7059	Intermediate Similarity	NPD7903	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD3323	Discontinued
0.7043	Intermediate Similarity	NPD1403	Approved
0.7043	Intermediate Similarity	NPD1404	Approved
0.7039	Intermediate Similarity	NPD5426	Phase 3
0.7037	Intermediate Similarity	NPD2185	Clinical (unspecified phase)
0.7037	Intermediate Similarity	NPD2641	Approved
0.7037	Intermediate Similarity	NPD2640	Approved
0.7033	Intermediate Similarity	NPD7998	Clinical (unspecified phase)
0.7015	Intermediate Similarity	NPD4998	Phase 3
0.7015	Intermediate Similarity	NPD7619	Phase 3
0.7015	Intermediate Similarity	NPD7618	Phase 3
0.7015	Intermediate Similarity	NPD4999	Phase 3
0.6984	Remote Similarity	NPD2642	Approved
0.6984	Remote Similarity	NPD2639	Approved
0.6983	Remote Similarity	NPD2007	Clinical (unspecified phase)
0.6974	Remote Similarity	NPD1708	Approved
0.6974	Remote Similarity	NPD1707	Approved
0.6974	Remote Similarity	NPD4649	Clinical (unspecified phase)
0.6973	Remote Similarity	NPD2150	Discontinued
0.697	Remote Similarity	NPD3002	Clinical (unspecified phase)
0.6965	Remote Similarity	NPD802	Phase 2
0.6963	Remote Similarity	NPD6828	Phase 2
0.6963	Remote Similarity	NPD6827	Clinical (unspecified phase)
0.6954	Remote Similarity	NPD1994	Approved
0.6954	Remote Similarity	NPD1993	Approved
0.6954	Remote Similarity	NPD1995	Approved
0.6948	Remote Similarity	NPD5612	Discontinued
0.6946	Remote Similarity	NPD3830	Phase 1
0.6939	Remote Similarity	NPD2391	Clinical (unspecified phase)
0.6939	Remote Similarity	NPD1332	Clinical (unspecified phase)
0.6934	Remote Similarity	NPD8094	Discontinued
0.6931	Remote Similarity	NPD7944	Discontinued
0.6931	Remote Similarity	NPD8113	Phase 2
0.6931	Remote Similarity	NPD5744	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD6217	Discontinued
0.6905	Remote Similarity	NPD6545	Clinical (unspecified phase)
0.69	Remote Similarity	NPD3871	Clinical (unspecified phase)
0.69	Remote Similarity	NPD3870	Clinical (unspecified phase)
0.6893	Remote Similarity	NPD4511	Phase 1
0.6893	Remote Similarity	NPD1262	Discovery
0.689	Remote Similarity	NPD6838	Clinical (unspecified phase)
0.6884	Remote Similarity	NPD8405	Clinical (unspecified phase)
0.6884	Remote Similarity	NPD6141	Clinical (unspecified phase)
0.6878	Remote Similarity	NPD5140	Approved
0.6878	Remote Similarity	NPD5138	Approved
0.6875	Remote Similarity	NPD3609	Approved
0.6875	Remote Similarity	NPD3610	Approved
0.6872	Remote Similarity	NPD3943	Clinical (unspecified phase)
0.6864	Remote Similarity	NPD6164	Phase 2
0.6864	Remote Similarity	NPD6165	Phase 2
0.6859	Remote Similarity	NPD4779	Clinical (unspecified phase)
0.6859	Remote Similarity	NPD7287	Clinical (unspecified phase)
0.6859	Remote Similarity	NPD2390	Clinical (unspecified phase)
0.6856	Remote Similarity	NPD5100	Phase 3
0.6854	Remote Similarity	NPD4341	Clinical (unspecified phase)
0.6837	Remote Similarity	NPD6277	Clinical (unspecified phase)
0.6834	Remote Similarity	NPD2872	Phase 2
0.6833	Remote Similarity	NPD1592	Phase 3
0.6832	Remote Similarity	NPD2127	Suspended
0.6831	Remote Similarity	NPD1661	Suspended
0.6825	Remote Similarity	NPD4520	Approved
0.6825	Remote Similarity	NPD972	Clinical (unspecified phase)
0.6825	Remote Similarity	NPD1853	Clinical (unspecified phase)
0.6823	Remote Similarity	NPD2875	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD3607	Clinical (unspecified phase)
0.6816	Remote Similarity	NPD5145	Clinical (unspecified phase)
0.6816	Remote Similarity	NPD4499	Approved
0.6814	Remote Similarity	NPD2960	Clinical (unspecified phase)
0.6812	Remote Similarity	NPD8629	Discontinued
0.6811	Remote Similarity	NPD3262	Approved
0.681	Remote Similarity	NPD4533	Clinical (unspecified phase)
0.6808	Remote Similarity	NPD8093	Discontinued
0.6806	Remote Similarity	NPD1248	Discontinued
0.6804	Remote Similarity	NPD6849	Phase 2
0.6804	Remote Similarity	NPD6850	Phase 2
0.6798	Remote Similarity	NPD5428	Discontinued
0.6796	Remote Similarity	NPD4047	Discontinued
0.6796	Remote Similarity	NPD4637	Clinical (unspecified phase)
0.6791	Remote Similarity	NPD2748	Clinical (unspecified phase)
0.6786	Remote Similarity	NPD3341	Clinical (unspecified phase)
0.6782	Remote Similarity	NPD6180	Clinical (unspecified phase)
0.6777	Remote Similarity	NPD4612	Discontinued
0.6771	Remote Similarity	NPD5021	Discontinued
0.6768	Remote Similarity	NPD5105	Approved
0.6768	Remote Similarity	NPD5106	Approved
0.6763	Remote Similarity	NPD991	Phase 2
0.6763	Remote Similarity	NPD992	Clinical (unspecified phase)
0.6762	Remote Similarity	NPD4023	Clinical (unspecified phase)
0.6759	Remote Similarity	NPD5409	Clinical (unspecified phase)
0.6758	Remote Similarity	NPD5254	Discontinued
0.6754	Remote Similarity	NPD4550	Clinical (unspecified phase)
0.6745	Remote Similarity	NPD2125	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD6481	Clinical (unspecified phase)
0.6732	Remote Similarity	NPD6278	Clinical (unspecified phase)
0.6729	Remote Similarity	NPD3330	Phase 1
0.672	Remote Similarity	NPD5255	Approved
0.6717	Remote Similarity	NPD8408	Discontinued
0.6717	Remote Similarity	NPD4891	Phase 2
0.6716	Remote Similarity	NPD5590	Clinical (unspecified phase)
0.6716	Remote Similarity	NPD3485	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