NPASS Compound

Structure

CID229173 OpenBabel06191716022D 34 40 0 0 1 0 0 0 0 0999 V2000 2.6831 2.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4013 -2.6361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8385 0.3174 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9890 -1.8271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4318 -0.5962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4067 -2.5316 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2507 1.1264 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5823 -0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4372 -0.7007 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5130 2.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6470 3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0850 1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0850 3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 2.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9511 1.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2562 1.0219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5130 1.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8495 0.1083 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 0.1910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7810 1.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9511 -0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6470 1.1910 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 -1.8549 0.2128 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 -0.3090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7810 2.6910 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 1 3 2 0 0 0 0 2 33 1 0 0 0 0 4 6 2 0 0 0 0 4 8 1 0 0 0 0 5 7 2 0 0 0 0 5 9 1 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 8 21 2 0 0 0 0 9 22 2 0 0 0 0 10 25 2 0 0 0 0 11 26 2 0 0 0 0 12 14 1 0 0 0 0 12 23 1 0 0 0 0 13 15 1 0 0 0 0 13 24 1 0 0 0 0 14 33 1 0 0 0 0 15 34 1 0 0 0 0 17 20 1 0 0 0 0 17 28 1 0 0 0 0 18 19 1 0 0 0 0 18 34 1 0 0 0 0 19 3 1 6 0 0 0 19 20 1 0 0 0 0 20 16 1 1 0 0 0 21 23 1 0 0 0 0 21 25 1 0 0 0 0 22 24 1 0 0 0 0 22 26 1 0 0 0 0 23 29 2 0 0 0 0 24 30 2 0 0 0 0 25 31 1 0 0 0 0 26 32 1 0 0 0 0 27 16 1 6 0 0 0 27 29 1 0 0 0 0 27 33 1 0 0 0 0 28 30 1 0 0 0 0 28 34 1 1 0 0 0 29 31 1 0 0 0 0 30 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	450.28
Volume:	487.8
LogP:	5.651
LogD:	4.634
LogS:	-4.893
# Rotatable Bonds:	3
TPSA:	38.06
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	7
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.376
Synthetic Accessibility Score:	4.112
Fsp3:	0.4
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-5.565
MDCK Permeability:	1.0955153811664786e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.998
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.292
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.985
Plasma Protein Binding (PPB):	95.45497131347656%
Volume Distribution (VD):	2.734
Pgp-substrate:	3.1372950077056885%

ADMET: Metabolism

CYP1A2-inhibitor:	0.469
CYP1A2-substrate:	0.957
CYP2C19-inhibitor:	0.4
CYP2C19-substrate:	0.895
CYP2C9-inhibitor:	0.064
CYP2C9-substrate:	0.168
CYP2D6-inhibitor:	0.933
CYP2D6-substrate:	0.942
CYP3A4-inhibitor:	0.332
CYP3A4-substrate:	0.925

ADMET: Excretion

Clearance (CL):	4.491
Half-life (T1/2):	0.149

ADMET: Toxicity

hERG Blockers:	0.98
Human Hepatotoxicity (H-HT):	0.291
Drug-inuced Liver Injury (DILI):	0.403
AMES Toxicity:	0.19
Rat Oral Acute Toxicity:	0.969
Maximum Recommended Daily Dose:	0.995
Skin Sensitization:	0.834
Carcinogencity:	0.356
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.989

Download Data

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

Natural Product: NPC229173

Natural Product ID:	NPC229173
*Common Name:**	Usambarine
IUPAC Name:	(2S,3R,12bS)-3-ethenyl-2-[[(1S)-2-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]methyl]-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine
Synonyms:	Usambarine
Standard InCHIKey:	JICXOAIUPFUZPK-DXBSEXLMSA-N
Standard InCHI:	InChI=1S/C30H34N4/c1-3-19-18-34-15-13-24-22-9-5-7-11-26(22)32-30(24)28(34)17-20(19)16-27-29-23(12-14-33(27)2)21-8-4-6-10-25(21)31-29/h3-11,19-20,27-28,31-32H,1,12-18H2,2H3/t19-,20-,27-,28-/m0/s1
SMILES:	C=C[C@H]1CN2CCc3c4ccccc4[nH]c3[C@@H]2C[C@@H]1C[C@H]1c2c(CCN1C)c1ccccc1[nH]2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1214432
PubChem CID:	442121
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
NPO18713	Strychnos usambarensis	Species	Loganiaceae	Eukaryota	roots	n.a.	n.a.	PMID[10217724]
NPO18713	Strychnos usambarensis	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12398531]
NPO18713	Strychnos usambarensis	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO18713	Strychnos usambarensis	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18713	Strychnos usambarensis	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18713	Strychnos usambarensis	Species	Loganiaceae	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	4
Others	2

Activity Type	# Activity
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	2360.0	nM	PMID[479355]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	2500.0	nM	PMID[479355]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC90	=	7290.0	nM	PMID[479355]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC90	=	9210.0	nM	PMID[479355]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.0	nM	PMID[479356]
NPT992	Organism	Entamoeba histolytica	Entamoeba histolytica	IC50	=	0.46	ug.mL-1	PMID[479357]

☑ 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 NPC229173 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	909
0.1-0.2	9504
0.2-0.3	20865
0.3-0.4	5422
0.4-0.5	2682
0.5-0.6	1758
0.6-0.7	1112
0.7-0.8	382
0.8-0.85	44
0.85-0.9	13
0.9-0.95	5
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9797	High Similarity	NPC474880
0.9797	High Similarity	NPC221786
0.9608	High Similarity	NPC474897
0.9533	High Similarity	NPC475990
0.9241	High Similarity	NPC280852
0.8912	High Similarity	NPC88097
0.8639	High Similarity	NPC198988
0.8627	High Similarity	NPC21605
0.8581	High Similarity	NPC325252
0.8543	High Similarity	NPC63157
0.8543	High Similarity	NPC473868
0.8516	High Similarity	NPC53947
0.8477	Intermediate Similarity	NPC59084
0.8452	Intermediate Similarity	NPC472294
0.8397	Intermediate Similarity	NPC33421
0.8355	Intermediate Similarity	NPC2949
0.8355	Intermediate Similarity	NPC115611
0.8344	Intermediate Similarity	NPC470233
0.8323	Intermediate Similarity	NPC288838
0.8303	Intermediate Similarity	NPC472123
0.8291	Intermediate Similarity	NPC325903
0.8272	Intermediate Similarity	NPC317105
0.8272	Intermediate Similarity	NPC271797
0.8272	Intermediate Similarity	NPC21174
0.8258	Intermediate Similarity	NPC204141
0.825	Intermediate Similarity	NPC216643
0.8247	Intermediate Similarity	NPC20144
0.8239	Intermediate Similarity	NPC476219
0.8235	Intermediate Similarity	NPC284635
0.8212	Intermediate Similarity	NPC218268
0.8193	Intermediate Similarity	NPC161861
0.8188	Intermediate Similarity	NPC475450
0.8153	Intermediate Similarity	NPC201380
0.8153	Intermediate Similarity	NPC179787
0.8141	Intermediate Similarity	NPC470440
0.8133	Intermediate Similarity	NPC473930
0.8121	Intermediate Similarity	NPC475428
0.8121	Intermediate Similarity	NPC22079
0.8103	Intermediate Similarity	NPC231536
0.8101	Intermediate Similarity	NPC321911
0.8095	Intermediate Similarity	NPC250361
0.8089	Intermediate Similarity	NPC63545
0.8086	Intermediate Similarity	NPC56765
0.8054	Intermediate Similarity	NPC473587
0.805	Intermediate Similarity	NPC40070
0.8038	Intermediate Similarity	NPC469811
0.8012	Intermediate Similarity	NPC317430
0.8	Intermediate Similarity	NPC469779
0.8	Intermediate Similarity	NPC469783
0.8	Intermediate Similarity	NPC469768
0.8	Intermediate Similarity	NPC469784
0.8	Intermediate Similarity	NPC469767
0.8	Intermediate Similarity	NPC469761
0.8	Intermediate Similarity	NPC469780
0.7987	Intermediate Similarity	NPC473762
0.7975	Intermediate Similarity	NPC135141
0.7975	Intermediate Similarity	NPC92796
0.7949	Intermediate Similarity	NPC469766
0.7947	Intermediate Similarity	NPC179365
0.7935	Intermediate Similarity	NPC73767
0.7927	Intermediate Similarity	NPC215584
0.7927	Intermediate Similarity	NPC44773
0.7901	Intermediate Similarity	NPC476297
0.7879	Intermediate Similarity	NPC470203
0.7866	Intermediate Similarity	NPC318065
0.7866	Intermediate Similarity	NPC206819
0.7861	Intermediate Similarity	NPC139291
0.7861	Intermediate Similarity	NPC472108
0.7823	Intermediate Similarity	NPC41174
0.7821	Intermediate Similarity	NPC110126
0.7821	Intermediate Similarity	NPC312092
0.7818	Intermediate Similarity	NPC122141
0.7818	Intermediate Similarity	NPC470204
0.7818	Intermediate Similarity	NPC81229
0.7818	Intermediate Similarity	NPC255229
0.7812	Intermediate Similarity	NPC477134
0.7806	Intermediate Similarity	NPC84911
0.7805	Intermediate Similarity	NPC236711
0.7797	Intermediate Similarity	NPC469501
0.7797	Intermediate Similarity	NPC469470
0.7796	Intermediate Similarity	NPC87755
0.7771	Intermediate Similarity	NPC194881
0.7765	Intermediate Similarity	NPC477611
0.7759	Intermediate Similarity	NPC470205
0.7758	Intermediate Similarity	NPC41257
0.7742	Intermediate Similarity	NPC261195
0.7742	Intermediate Similarity	NPC96102
0.7742	Intermediate Similarity	NPC29886
0.7733	Intermediate Similarity	NPC59269
0.7713	Intermediate Similarity	NPC475422
0.7713	Intermediate Similarity	NPC126066
0.7706	Intermediate Similarity	NPC201634
0.7697	Intermediate Similarity	NPC286427
0.7692	Intermediate Similarity	NPC105127
0.7692	Intermediate Similarity	NPC251722
0.7692	Intermediate Similarity	NPC125746
0.7692	Intermediate Similarity	NPC314102
0.7679	Intermediate Similarity	NPC2165
0.7679	Intermediate Similarity	NPC195507
0.7674	Intermediate Similarity	NPC474958
0.767	Intermediate Similarity	NPC99939
0.767	Intermediate Similarity	NPC308931
0.767	Intermediate Similarity	NPC15102
0.7654	Intermediate Similarity	NPC37548
0.7647	Intermediate Similarity	NPC477065
0.7627	Intermediate Similarity	NPC17273
0.7627	Intermediate Similarity	NPC135601
0.7627	Intermediate Similarity	NPC141612
0.7619	Intermediate Similarity	NPC90723
0.7619	Intermediate Similarity	NPC247987
0.7616	Intermediate Similarity	NPC189812
0.7616	Intermediate Similarity	NPC329688
0.7607	Intermediate Similarity	NPC24678
0.7607	Intermediate Similarity	NPC105818
0.7602	Intermediate Similarity	NPC82331
0.7595	Intermediate Similarity	NPC104483
0.7593	Intermediate Similarity	NPC470111
0.7578	Intermediate Similarity	NPC314372
0.7566	Intermediate Similarity	NPC476116
0.7565	Intermediate Similarity	NPC476041
0.7565	Intermediate Similarity	NPC304926
0.7562	Intermediate Similarity	NPC190296
0.7557	Intermediate Similarity	NPC472109
0.7557	Intermediate Similarity	NPC472110
0.7551	Intermediate Similarity	NPC54102
0.7551	Intermediate Similarity	NPC162689
0.7547	Intermediate Similarity	NPC279081
0.7546	Intermediate Similarity	NPC2272
0.7544	Intermediate Similarity	NPC194411
0.7543	Intermediate Similarity	NPC314919
0.7531	Intermediate Similarity	NPC143872
0.7516	Intermediate Similarity	NPC242556
0.7515	Intermediate Similarity	NPC469763
0.7515	Intermediate Similarity	NPC469786
0.7515	Intermediate Similarity	NPC259644
0.7515	Intermediate Similarity	NPC469765
0.7515	Intermediate Similarity	NPC469760
0.7515	Intermediate Similarity	NPC25008
0.7515	Intermediate Similarity	NPC73952
0.7514	Intermediate Similarity	NPC315617
0.7514	Intermediate Similarity	NPC471579
0.7514	Intermediate Similarity	NPC316018
0.7514	Intermediate Similarity	NPC314058
0.7514	Intermediate Similarity	NPC316359
0.7513	Intermediate Similarity	NPC183407
0.75	Intermediate Similarity	NPC265576
0.75	Intermediate Similarity	NPC472112
0.7484	Intermediate Similarity	NPC82295
0.7483	Intermediate Similarity	NPC81561
0.7483	Intermediate Similarity	NPC122718
0.7471	Intermediate Similarity	NPC274229
0.747	Intermediate Similarity	NPC80597
0.747	Intermediate Similarity	NPC212376
0.747	Intermediate Similarity	NPC70922
0.747	Intermediate Similarity	NPC38736
0.747	Intermediate Similarity	NPC211572
0.747	Intermediate Similarity	NPC470507
0.747	Intermediate Similarity	NPC75540
0.746	Intermediate Similarity	NPC473362
0.746	Intermediate Similarity	NPC166492
0.7444	Intermediate Similarity	NPC102338
0.7444	Intermediate Similarity	NPC63199
0.7444	Intermediate Similarity	NPC111602
0.7444	Intermediate Similarity	NPC196251
0.7444	Intermediate Similarity	NPC175474
0.7443	Intermediate Similarity	NPC91179
0.7443	Intermediate Similarity	NPC472105
0.7443	Intermediate Similarity	NPC187827
0.7442	Intermediate Similarity	NPC97343
0.7439	Intermediate Similarity	NPC187951
0.7438	Intermediate Similarity	NPC230002
0.743	Intermediate Similarity	NPC94752
0.7427	Intermediate Similarity	NPC160105
0.7425	Intermediate Similarity	NPC285469
0.7418	Intermediate Similarity	NPC472113
0.7415	Intermediate Similarity	NPC148140
0.7414	Intermediate Similarity	NPC37423
0.7414	Intermediate Similarity	NPC275305
0.7412	Intermediate Similarity	NPC8104
0.741	Intermediate Similarity	NPC200214
0.7405	Intermediate Similarity	NPC52557
0.7384	Intermediate Similarity	NPC63751
0.7381	Intermediate Similarity	NPC193740
0.7381	Intermediate Similarity	NPC167635
0.7378	Intermediate Similarity	NPC471957
0.7374	Intermediate Similarity	NPC133003
0.7371	Intermediate Similarity	NPC472122
0.7371	Intermediate Similarity	NPC24594
0.7362	Intermediate Similarity	NPC159856
0.736	Intermediate Similarity	NPC472104
0.736	Intermediate Similarity	NPC19679
0.7358	Intermediate Similarity	NPC150259
0.7353	Intermediate Similarity	NPC225018
0.7348	Intermediate Similarity	NPC213629
0.7345	Intermediate Similarity	NPC16659
0.7337	Intermediate Similarity	NPC6436
0.7333	Intermediate Similarity	NPC475915
0.7333	Intermediate Similarity	NPC124005
0.733	Intermediate Similarity	NPC68354
0.7326	Intermediate Similarity	NPC249040

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 NPC229173 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	393
0.1-0.2	677
0.2-0.3	1152
0.3-0.4	1867
0.4-0.5	2300
0.5-0.6	1923
0.6-0.7	688
0.7-0.8	136
0.8-0.85	13
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8609	High Similarity	NPD4637	Clinical (unspecified phase)
0.8355	Intermediate Similarity	NPD3943	Clinical (unspecified phase)
0.8291	Intermediate Similarity	NPD2837	Discontinued
0.8274	Intermediate Similarity	NPD6277	Clinical (unspecified phase)
0.8221	Intermediate Similarity	NPD5744	Clinical (unspecified phase)
0.8205	Intermediate Similarity	NPD1683	Approved
0.82	Intermediate Similarity	NPD3385	Approved
0.8194	Intermediate Similarity	NPD5254	Discontinued
0.816	Intermediate Similarity	NPD3323	Discontinued
0.8065	Intermediate Similarity	NPD1722	Approved
0.7987	Intermediate Similarity	NPD4374	Clinical (unspecified phase)
0.7935	Intermediate Similarity	NPD786	Approved
0.7922	Intermediate Similarity	NPD6554	Approved
0.7922	Intermediate Similarity	NPD45	Approved
0.7917	Intermediate Similarity	NPD6828	Phase 2
0.7917	Intermediate Similarity	NPD6827	Clinical (unspecified phase)
0.7879	Intermediate Similarity	NPD1853	Clinical (unspecified phase)
0.7874	Intermediate Similarity	NPD6610	Clinical (unspecified phase)
0.787	Intermediate Similarity	NPD4112	Clinical (unspecified phase)
0.7836	Intermediate Similarity	NPD4181	Approved
0.7826	Intermediate Similarity	NPD2172	Phase 1
0.7826	Intermediate Similarity	NPD4462	Approved
0.7826	Intermediate Similarity	NPD4463	Approved
0.7812	Intermediate Similarity	NPD4547	Phase 3
0.7806	Intermediate Similarity	NPD1262	Discovery
0.7798	Intermediate Similarity	NPD4779	Clinical (unspecified phase)
0.7764	Intermediate Similarity	NPD3100	Discontinued
0.7746	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.7742	Intermediate Similarity	NPD198	Clinical (unspecified phase)
0.7733	Intermediate Similarity	NPD7111	Discontinued
0.7706	Intermediate Similarity	NPD3609	Approved
0.7706	Intermediate Similarity	NPD3610	Approved
0.7697	Intermediate Similarity	NPD3654	Approved
0.7644	Intermediate Similarity	NPD6595	Phase 3
0.763	Intermediate Similarity	NPD6203	Clinical (unspecified phase)
0.7628	Intermediate Similarity	NPD1254	Approved
0.7628	Intermediate Similarity	NPD1255	Approved
0.7628	Intermediate Similarity	NPD1253	Approved
0.7628	Intermediate Similarity	NPD1256	Approved
0.7616	Intermediate Similarity	NPD4128	Approved
0.7584	Intermediate Similarity	NPD5787	Discontinued
0.7576	Intermediate Similarity	NPD6285	Phase 2
0.7564	Intermediate Similarity	NPD4880	Discontinued
0.7562	Intermediate Similarity	NPD4047	Discontinued
0.7543	Intermediate Similarity	NPD5473	Discontinued
0.7543	Intermediate Similarity	NPD5962	Phase 2
0.7531	Intermediate Similarity	NPD7469	Discontinued
0.753	Intermediate Similarity	NPD2150	Discontinued
0.7514	Intermediate Similarity	NPD5065	Approved
0.75	Intermediate Similarity	NPD3835	Phase 3
0.75	Intermediate Similarity	NPD3833	Phase 3
0.7486	Intermediate Similarity	NPD6278	Clinical (unspecified phase)
0.7486	Intermediate Similarity	NPD2960	Clinical (unspecified phase)
0.7485	Intermediate Similarity	NPD2641	Approved
0.7485	Intermediate Similarity	NPD2185	Clinical (unspecified phase)
0.7485	Intermediate Similarity	NPD2640	Approved
0.7485	Intermediate Similarity	NPD4326	Phase 2
0.7468	Intermediate Similarity	NPD947	Approved
0.7457	Intermediate Similarity	NPD7216	Approved
0.7457	Intermediate Similarity	NPD7217	Approved
0.745	Intermediate Similarity	NPD4811	Discontinued
0.7439	Intermediate Similarity	NPD5538	Clinical (unspecified phase)
0.743	Intermediate Similarity	NPD6217	Discontinued
0.7427	Intermediate Similarity	NPD2639	Approved
0.7427	Intermediate Similarity	NPD2642	Approved
0.7423	Intermediate Similarity	NPD1528	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD3401	Clinical (unspecified phase)
0.7401	Intermediate Similarity	NPD1895	Discontinued
0.7389	Intermediate Similarity	NPD3486	Clinical (unspecified phase)
0.7389	Intermediate Similarity	NPD3961	Discontinued
0.7384	Intermediate Similarity	NPD2390	Clinical (unspecified phase)
0.7371	Intermediate Similarity	NPD4075	Phase 2
0.736	Intermediate Similarity	NPD5106	Approved
0.736	Intermediate Similarity	NPD5105	Approved
0.7353	Intermediate Similarity	NPD5315	Discontinued
0.7346	Intermediate Similarity	NPD2006	Phase 2
0.7338	Intermediate Similarity	NPD2119	Approved
0.7338	Intermediate Similarity	NPD2118	Approved
0.7337	Intermediate Similarity	NPD7619	Phase 3
0.7337	Intermediate Similarity	NPD7618	Phase 3
0.7337	Intermediate Similarity	NPD5418	Discontinued
0.7333	Intermediate Similarity	NPD2430	Phase 2
0.733	Intermediate Similarity	NPD3505	Approved
0.733	Intermediate Similarity	NPD3506	Approved
0.7318	Intermediate Similarity	NPD7564	Discontinued
0.7308	Intermediate Similarity	NPD3475	Approved
0.7308	Intermediate Similarity	NPD5145	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD3476	Approved
0.7303	Intermediate Similarity	NPD4649	Clinical (unspecified phase)
0.7301	Intermediate Similarity	NPD4509	Discontinued
0.7293	Intermediate Similarity	NPD7394	Phase 2
0.7293	Intermediate Similarity	NPD8431	Approved
0.7288	Intermediate Similarity	NPD4079	Approved
0.7288	Intermediate Similarity	NPD3341	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD4076	Approved
0.7283	Intermediate Similarity	NPD5069	Clinical (unspecified phase)
0.7283	Intermediate Similarity	NPD5021	Discontinued
0.7278	Intermediate Similarity	NPD3944	Approved
0.7278	Intermediate Similarity	NPD3942	Approved
0.7261	Intermediate Similarity	NPD1251	Discontinued
0.7251	Intermediate Similarity	NPD6771	Discontinued
0.7246	Intermediate Similarity	NPD2882	Phase 1
0.7246	Intermediate Similarity	NPD6476	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD6158	Phase 2
0.7241	Intermediate Similarity	NPD5436	Phase 1
0.7241	Intermediate Similarity	NPD4184	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD2007	Clinical (unspecified phase)
0.7238	Intermediate Similarity	NPD2793	Discontinued
0.7238	Intermediate Similarity	NPD4426	Clinical (unspecified phase)
0.7234	Intermediate Similarity	NPD4601	Approved
0.7234	Intermediate Similarity	NPD4600	Approved
0.7219	Intermediate Similarity	NPD2927	Phase 3
0.7219	Intermediate Similarity	NPD2580	Discontinued
0.7209	Intermediate Similarity	NPD5140	Approved
0.7209	Intermediate Similarity	NPD5138	Approved
0.7207	Intermediate Similarity	NPD7867	Phase 1
0.7207	Intermediate Similarity	NPD1707	Approved
0.7207	Intermediate Similarity	NPD1708	Approved
0.7198	Intermediate Similarity	NPD6141	Clinical (unspecified phase)
0.7197	Intermediate Similarity	NPD715	Phase 3
0.7193	Intermediate Similarity	NPD1404	Approved
0.7193	Intermediate Similarity	NPD6454	Clinical (unspecified phase)
0.7193	Intermediate Similarity	NPD1403	Approved
0.7175	Intermediate Similarity	NPD5104	Approved
0.7174	Intermediate Similarity	NPD6630	Clinical (unspecified phase)
0.717	Intermediate Similarity	NPD4030	Approved
0.717	Intermediate Similarity	NPD4029	Approved
0.717	Intermediate Similarity	NPD4028	Approved
0.7168	Intermediate Similarity	NPD2915	Discontinued
0.7168	Intermediate Similarity	NPD4550	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD1332	Clinical (unspecified phase)
0.7166	Intermediate Similarity	NPD2880	Discontinued
0.716	Intermediate Similarity	NPD977	Approved
0.716	Intermediate Similarity	NPD975	Approved
0.716	Intermediate Similarity	NPD976	Approved
0.7158	Intermediate Similarity	NPD8110	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD3015	Discontinued
0.7143	Intermediate Similarity	NPD4500	Approved
0.7143	Intermediate Similarity	NPD1325	Approved
0.7143	Intermediate Similarity	NPD4501	Approved
0.7143	Intermediate Similarity	NPD1326	Approved
0.7135	Intermediate Similarity	NPD7722	Suspended
0.7115	Intermediate Similarity	NPD992	Clinical (unspecified phase)
0.7115	Intermediate Similarity	NPD991	Phase 2
0.7112	Intermediate Similarity	NPD6449	Clinical (unspecified phase)
0.7104	Intermediate Similarity	NPD5590	Clinical (unspecified phase)
0.7098	Intermediate Similarity	NPD8493	Clinical (unspecified phase)
0.7098	Intermediate Similarity	NPD8322	Phase 2
0.7098	Intermediate Similarity	NPD6838	Clinical (unspecified phase)
0.7095	Intermediate Similarity	NPD40	Phase 2
0.7095	Intermediate Similarity	NPD8386	Phase 2
0.7095	Intermediate Similarity	NPD2930	Clinical (unspecified phase)
0.7095	Intermediate Similarity	NPD5730	Phase 2
0.7091	Intermediate Similarity	NPD5671	Approved
0.7091	Intermediate Similarity	NPD1918	Clinical (unspecified phase)
0.7079	Intermediate Similarity	NPD6375	Clinical (unspecified phase)
0.7074	Intermediate Similarity	NPD6664	Approved
0.7069	Intermediate Similarity	NPD1313	Approved
0.7053	Intermediate Similarity	NPD6816	Phase 3
0.7049	Intermediate Similarity	NPD3378	Clinical (unspecified phase)
0.7044	Intermediate Similarity	NPD803	Phase 1
0.7043	Intermediate Similarity	NPD4615	Phase 2
0.7039	Intermediate Similarity	NPD2144	Approved
0.7029	Intermediate Similarity	NPD2392	Clinical (unspecified phase)
0.7029	Intermediate Similarity	NPD6794	Approved
0.7027	Intermediate Similarity	NPD4499	Approved
0.7022	Intermediate Similarity	NPD3799	Suspended
0.7022	Intermediate Similarity	NPD6492	Phase 2
0.7018	Intermediate Similarity	NPD3114	Approved
0.7018	Intermediate Similarity	NPD3112	Approved
0.7018	Intermediate Similarity	NPD3113	Approved
0.7018	Intermediate Similarity	NPD3115	Approved
0.7017	Intermediate Similarity	NPD3038	Discontinued
0.7005	Intermediate Similarity	NPD7594	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7621	Clinical (unspecified phase)
0.6995	Remote Similarity	NPD5426	Phase 3
0.6989	Remote Similarity	NPD6180	Clinical (unspecified phase)
0.6989	Remote Similarity	NPD6761	Discontinued
0.6984	Remote Similarity	NPD5462	Discontinued
0.6983	Remote Similarity	NPD3348	Phase 2
0.6978	Remote Similarity	NPD4441	Phase 2
0.6977	Remote Similarity	NPD1192	Clinical (unspecified phase)
0.6977	Remote Similarity	NPD2865	Clinical (unspecified phase)
0.6977	Remote Similarity	NPD6497	Approved
0.6971	Remote Similarity	NPD1002	Clinical (unspecified phase)
0.697	Remote Similarity	NPD1592	Phase 3
0.6959	Remote Similarity	NPD4023	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD2165	Phase 1
0.6954	Remote Similarity	NPD7481	Approved
0.6954	Remote Similarity	NPD2385	Clinical (unspecified phase)
0.6954	Remote Similarity	NPD7480	Approved
0.6951	Remote Similarity	NPD768	Clinical (unspecified phase)
0.6947	Remote Similarity	NPD3230	Clinical (unspecified phase)
0.6947	Remote Similarity	NPD6468	Clinical (unspecified phase)
0.6947	Remote Similarity	NPD6469	Phase 3
0.694	Remote Similarity	NPD3607	Clinical (unspecified phase)
0.694	Remote Similarity	NPD4957	Phase 2
0.694	Remote Similarity	NPD5892	Approved
0.694	Remote Similarity	NPD6178	Phase 3

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