NPASS Compound

Structure

NPC473391 OpenBabel07101718292D 23 24 0 0 0 0 0 0 0 0999 V2000 6.9282 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 21 1 0 0 0 0 2 22 1 0 0 0 0 3 23 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 5 12 1 0 0 0 0 6 13 2 0 0 0 0 7 8 2 0 0 0 0 7 12 1 0 0 0 0 8 15 1 0 0 0 0 9 12 2 0 0 0 0 9 13 1 0 0 0 0 10 14 2 0 0 0 0 10 16 1 0 0 0 0 11 14 1 0 0 0 0 11 17 2 0 0 0 0 13 21 1 0 0 0 0 14 22 1 0 0 0 0 15 18 1 0 0 0 0 15 19 2 0 0 0 0 16 18 2 0 0 0 0 16 20 1 0 0 0 0 17 18 1 0 0 0 0 17 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	314.12
Volume:	325.631
LogP:	3.509
LogD:	3.361
LogS:	-5.296
# Rotatable Bonds:	6
TPSA:	64.99
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.654
Synthetic Accessibility Score:	2.101
Fsp3:	0.167
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.882
MDCK Permeability:	1.6692112694727257e-05
Pgp-inhibitor:	0.049
Pgp-substrate:	0.395
Human Intestinal Absorption (HIA):	0.012
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.67

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.17
Plasma Protein Binding (PPB):	95.40160369873047%
Volume Distribution (VD):	0.512
Pgp-substrate:	2.6478233337402344%

ADMET: Metabolism

CYP1A2-inhibitor:	0.981
CYP1A2-substrate:	0.923
CYP2C19-inhibitor:	0.926
CYP2C19-substrate:	0.297
CYP2C9-inhibitor:	0.666
CYP2C9-substrate:	0.961
CYP2D6-inhibitor:	0.691
CYP2D6-substrate:	0.926
CYP3A4-inhibitor:	0.927
CYP3A4-substrate:	0.318

ADMET: Excretion

Clearance (CL):	10.783
Half-life (T1/2):	0.447

ADMET: Toxicity

hERG Blockers:	0.15
Human Hepatotoxicity (H-HT):	0.117
Drug-inuced Liver Injury (DILI):	0.783
AMES Toxicity:	0.302
Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.52
Skin Sensitization:	0.892
Carcinogencity:	0.345
Eye Corrosion:	0.026
Eye Irritation:	0.98
Respiratory Toxicity:	0.839

Download Data

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

Natural Product: NPC473391

Natural Product ID:	NPC473391
*Common Name:**	2'-Hydroxy-3,4',6'-Trimethoxychalcone
IUPAC Name:	(E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(3-methoxyphenyl)prop-2-en-1-one
Synonyms:
Standard InCHIKey:	AOXAMOYDMUNFNC-BQYQJAHWSA-N
Standard InCHI:	InChI=1S/C18H18O5/c1-21-13-6-4-5-12(9-13)7-8-15(19)18-16(20)10-14(22-2)11-17(18)23-3/h4-11,20H,1-3H3/b8-7+
SMILES:	COc1cccc(c1)/C=C/C(=O)c1c(O)cc(cc1OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL406837
PubChem CID:	14034811
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003467] Linear 1,3-diarylpropanoids [CHEMONTID:0001630] Chalcones and dihydrochalcones [CHEMONTID:0003472] 2'-Hydroxychalcones

*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
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11830162]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12809361]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	root	n.a.	n.a.	PMID[25597012]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26193	Piper methysticum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26193	Piper methysticum	Species	Piperaceae	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	15
Others	51

Activity Type	# Activity
Cell Line	50
Individual Protein	3
NON-MOLECULAR	1
Others	12

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT111	Cell Line	K562	Homo sapiens	Activity	=	52.0	%	PMID[491733]
NPT1422	Individual Protein	ATP-binding cassette sub-family G member 2	Homo sapiens	Inhibition	=	93.0	%	PMID[491734]
NPT1422	Individual Protein	ATP-binding cassette sub-family G member 2	Homo sapiens	Inhibition	=	97.9	%	PMID[491734]
NPT1422	Individual Protein	ATP-binding cassette sub-family G member 2	Homo sapiens	IC50	=	260.0	nM	PMID[491734]
NPT71	Cell Line	HEK293	Homo sapiens	IG50	=	10.0	uM	PMID[491734]
NPT1229	Cell Line	Huh-7	Homo sapiens	Survival	=	13.0	%	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	Survival	=	1.0	%	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Survival	=	11.0	%	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	Survival	=	0.0	%	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	Survival	=	22.0	%	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Survival	=	1.0	%	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	Survival	=	7.0	%	PMID[491736]
NPT1229	Cell Line	Huh-7	Homo sapiens	IC50	=	15000.0	nM	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	IC50	=	11200.0	nM	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	13200.0	nM	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	7700.0	nM	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	7300.0	nM	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	IC50	=	14800.0	nM	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	IC50	=	10400.0	nM	PMID[491736]
NPT2186	Cell Line	RL	Homo sapiens	IC50	=	9000.0	nM	PMID[491736]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	10300.0	nM	PMID[491736]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity_index	=	1.6	n.a.	PMID[491736]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	56.0	%	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	Activity_index	=	14.4	n.a.	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	Activity	=	31.0	%	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Activity_index	=	4.2	n.a.	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Activity	=	54.0	%	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	Activity_index	=	1.2	n.a.	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	Activity	=	30.0	%	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	Activity_index	=	4.4	n.a.	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	Activity	=	39.0	%	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Activity_index	=	1.2	n.a.	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Activity	=	35.0	%	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	Activity_index	=	2.6	n.a.	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	Activity	=	49.0	%	PMID[491736]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity_index	=	0.1	n.a.	PMID[491736]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	8.5	%	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	Activity_index	=	6.1	n.a.	PMID[491736]
NPT492	Cell Line	Caco-2	Homo sapiens	Activity	=	34.0	%	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Activity_index	=	3.6	n.a.	PMID[491736]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Activity	=	38.0	%	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	Activity_index	=	0.3	n.a.	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	Activity	=	37.0	%	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	Activity_index	=	0.4	n.a.	PMID[491736]
NPT306	Cell Line	PC-3	Homo sapiens	Activity	=	9.4	%	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Activity_index	=	0.1	n.a.	PMID[491736]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Activity	=	1.4	%	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	Activity_index	=	0.1	n.a.	PMID[491736]
NPT941	Cell Line	HaCaT	Homo sapiens	Activity	=	8.0	%	PMID[491736]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	3100.0	nM	PMID[491737]
NPT113	Cell Line	RAW264.7	Mus musculus	Inhibition	=	86.9	%	PMID[491738]
NPT113	Cell Line	RAW264.7	Mus musculus	IC50	=	2400.0	nM	PMID[491738]
NPT113	Cell Line	RAW264.7	Mus musculus	IC50	=	34000.0	nM	PMID[491738]
NPT27	Others	Unspecified		TI	=	38.0	n.a.	PMID[491734]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	3100.0	nM	PMID[491735]
NPT2	Others	Unspecified		Survival	=	44.0	%	PMID[491736]
NPT2	Others	Unspecified		IC50	>	20000.0	nM	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	1.8	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	2.4	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	2.0	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	3.5	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	3.7	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	2.6	n.a.	PMID[491736]
NPT2	Others	Unspecified		Ratio IC50	=	3.0	n.a.	PMID[491736]

☑ 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 NPC473391 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	349
0.1-0.2	1700
0.2-0.3	4396
0.3-0.4	11020
0.4-0.5	6692
0.5-0.6	3644
0.6-0.7	5431
0.7-0.8	5758
0.8-0.85	2279
0.85-0.9	1116
0.9-0.95	264
0.95-1	48

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC472364
0.9769	High Similarity	NPC139813
0.9769	High Similarity	NPC175098
0.9769	High Similarity	NPC337373
0.9769	High Similarity	NPC192304
0.9769	High Similarity	NPC56031
0.9769	High Similarity	NPC472365
0.9769	High Similarity	NPC263670
0.9769	High Similarity	NPC312318
0.9769	High Similarity	NPC242294
0.9769	High Similarity	NPC188646
0.9695	High Similarity	NPC286336
0.9692	High Similarity	NPC212631
0.9692	High Similarity	NPC129132
0.9692	High Similarity	NPC205468
0.9692	High Similarity	NPC257756
0.9692	High Similarity	NPC87231
0.963	High Similarity	NPC49108
0.9627	High Similarity	NPC109232
0.9618	High Similarity	NPC159623
0.9618	High Similarity	NPC144051
0.9618	High Similarity	NPC28753
0.9618	High Similarity	NPC18877
0.9618	High Similarity	NPC204960
0.9618	High Similarity	NPC20560
0.9618	High Similarity	NPC82225
0.9618	High Similarity	NPC294593
0.9615	High Similarity	NPC308037
0.9615	High Similarity	NPC64359
0.9615	High Similarity	NPC262359
0.9559	High Similarity	NPC119663
0.9559	High Similarity	NPC471417
0.9552	High Similarity	NPC21350
0.9549	High Similarity	NPC66349
0.9549	High Similarity	NPC249606
0.9549	High Similarity	NPC477244
0.9549	High Similarity	NPC477243
0.9549	High Similarity	NPC12165
0.9549	High Similarity	NPC150399
0.9549	High Similarity	NPC41461
0.9549	High Similarity	NPC25287
0.9549	High Similarity	NPC213603
0.9549	High Similarity	NPC472367
0.9549	High Similarity	NPC1486
0.9549	High Similarity	NPC98115
0.9549	High Similarity	NPC186838
0.9549	High Similarity	NPC476333
0.9549	High Similarity	NPC477242
0.9549	High Similarity	NPC168105
0.9549	High Similarity	NPC274109
0.9485	High Similarity	NPC284556
0.9485	High Similarity	NPC301178
0.9481	High Similarity	NPC477956
0.9478	High Similarity	NPC209560
0.9478	High Similarity	NPC294409
0.9478	High Similarity	NPC181124
0.9478	High Similarity	NPC162680
0.9478	High Similarity	NPC7013
0.9478	High Similarity	NPC472419
0.9478	High Similarity	NPC212767
0.9478	High Similarity	NPC317119
0.9478	High Similarity	NPC303644
0.9478	High Similarity	NPC153979
0.9478	High Similarity	NPC188879
0.9478	High Similarity	NPC116632
0.9474	High Similarity	NPC156092
0.9474	High Similarity	NPC13575
0.9474	High Similarity	NPC131039
0.9466	High Similarity	NPC189106
0.9466	High Similarity	NPC475008
0.9466	High Similarity	NPC128348
0.9466	High Similarity	NPC309717
0.9466	High Similarity	NPC66384
0.9466	High Similarity	NPC186097
0.9466	High Similarity	NPC475009
0.9466	High Similarity	NPC112192
0.9466	High Similarity	NPC164236
0.9466	High Similarity	NPC313618
0.9462	High Similarity	NPC247779
0.9412	High Similarity	NPC144118
0.9412	High Similarity	NPC326109
0.9412	High Similarity	NPC215311
0.9412	High Similarity	NPC80962
0.9412	High Similarity	NPC213659
0.9412	High Similarity	NPC259166
0.9412	High Similarity	NPC48624
0.9412	High Similarity	NPC11056
0.9412	High Similarity	NPC219917
0.9412	High Similarity	NPC172250
0.9412	High Similarity	NPC204985
0.9407	High Similarity	NPC309154
0.9407	High Similarity	NPC472368
0.9407	High Similarity	NPC12175
0.9407	High Similarity	NPC124269
0.9407	High Similarity	NPC55162
0.9407	High Similarity	NPC90665
0.9407	High Similarity	NPC279668
0.9407	High Similarity	NPC278323
0.9403	High Similarity	NPC193792
0.9403	High Similarity	NPC240593
0.9398	High Similarity	NPC103842
0.9385	High Similarity	NPC211120
0.9353	High Similarity	NPC99454
0.9353	High Similarity	NPC130176
0.9353	High Similarity	NPC196114
0.9343	High Similarity	NPC268204
0.9343	High Similarity	NPC321980
0.9343	High Similarity	NPC52789
0.9343	High Similarity	NPC469404
0.9343	High Similarity	NPC26051
0.9343	High Similarity	NPC55832
0.9343	High Similarity	NPC470087
0.9343	High Similarity	NPC470089
0.9343	High Similarity	NPC250755
0.9338	High Similarity	NPC283429
0.9338	High Similarity	NPC470211
0.9338	High Similarity	NPC472366
0.9338	High Similarity	NPC295384
0.9333	High Similarity	NPC250266
0.9333	High Similarity	NPC266597
0.9328	High Similarity	NPC234560
0.9328	High Similarity	NPC39426
0.9323	High Similarity	NPC27643
0.9308	High Similarity	NPC80694
0.9308	High Similarity	NPC186098
0.9286	High Similarity	NPC119660
0.9286	High Similarity	NPC93034
0.9275	High Similarity	NPC254659
0.9275	High Similarity	NPC287722
0.927	High Similarity	NPC101366
0.927	High Similarity	NPC253822
0.927	High Similarity	NPC265178
0.9265	High Similarity	NPC251681
0.9265	High Similarity	NPC188947
0.9265	High Similarity	NPC99333
0.9265	High Similarity	NPC471620
0.9265	High Similarity	NPC243528
0.9265	High Similarity	NPC280284
0.9259	High Similarity	NPC47815
0.9259	High Similarity	NPC194281
0.9259	High Similarity	NPC87545
0.9259	High Similarity	NPC24394
0.9259	High Similarity	NPC473887
0.9259	High Similarity	NPC235428
0.9259	High Similarity	NPC29353
0.9259	High Similarity	NPC13408
0.9259	High Similarity	NPC234133
0.9259	High Similarity	NPC124784
0.9259	High Similarity	NPC231772
0.9259	High Similarity	NPC127447
0.9231	High Similarity	NPC128428
0.9231	High Similarity	NPC305518
0.9214	High Similarity	NPC12377
0.9209	High Similarity	NPC166138
0.9209	High Similarity	NPC301751
0.9209	High Similarity	NPC51887
0.9209	High Similarity	NPC18585
0.9209	High Similarity	NPC245482
0.9209	High Similarity	NPC106985
0.9209	High Similarity	NPC142165
0.9209	High Similarity	NPC117836
0.9209	High Similarity	NPC476178
0.9209	High Similarity	NPC475705
0.9203	High Similarity	NPC126534
0.9203	High Similarity	NPC232021
0.9203	High Similarity	NPC110969
0.9203	High Similarity	NPC40118
0.9191	High Similarity	NPC275055
0.9191	High Similarity	NPC44573
0.9191	High Similarity	NPC290291
0.9191	High Similarity	NPC23870
0.9191	High Similarity	NPC228661
0.9179	High Similarity	NPC223354
0.9167	High Similarity	NPC185497
0.9155	High Similarity	NPC474052
0.9155	High Similarity	NPC92722
0.9155	High Similarity	NPC38545
0.9155	High Similarity	NPC102003
0.9155	High Similarity	NPC171916
0.9155	High Similarity	NPC266499
0.9143	High Similarity	NPC328623
0.9143	High Similarity	NPC234629
0.9143	High Similarity	NPC476055
0.9143	High Similarity	NPC311741
0.9137	High Similarity	NPC297600
0.9137	High Similarity	NPC11561
0.9137	High Similarity	NPC202981
0.9137	High Similarity	NPC226636
0.9137	High Similarity	NPC144499
0.9137	High Similarity	NPC73028
0.9137	High Similarity	NPC84266
0.9137	High Similarity	NPC1534
0.9137	High Similarity	NPC310340
0.9137	High Similarity	NPC148545
0.913	High Similarity	NPC159275
0.913	High Similarity	NPC129853
0.913	High Similarity	NPC110228
0.913	High Similarity	NPC269652
0.913	High Similarity	NPC261227
0.913	High Similarity	NPC241100

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 NPC473391 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	325
0.1-0.2	989
0.2-0.3	1528
0.3-0.4	2628
0.4-0.5	1866
0.5-0.6	1166
0.6-0.7	449
0.7-0.8	144
0.8-0.85	41
0.85-0.9	9
0.9-0.95	4
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9466	High Similarity	NPD1240	Approved
0.9328	High Similarity	NPD1510	Phase 2
0.9323	High Similarity	NPD1607	Approved
0.9007	High Similarity	NPD4378	Clinical (unspecified phase)
0.8986	High Similarity	NPD1549	Phase 2
0.8913	High Similarity	NPD1552	Clinical (unspecified phase)
0.8913	High Similarity	NPD1550	Clinical (unspecified phase)
0.8849	High Similarity	NPD970	Clinical (unspecified phase)
0.8841	High Similarity	NPD2796	Approved
0.8803	High Similarity	NPD1511	Approved
0.8784	High Similarity	NPD3882	Suspended
0.8776	High Similarity	NPD2801	Approved
0.8776	High Similarity	NPD2393	Clinical (unspecified phase)
0.8741	High Similarity	NPD7410	Clinical (unspecified phase)
0.8707	High Similarity	NPD1934	Approved
0.8705	High Similarity	NPD2935	Discontinued
0.8699	High Similarity	NPD4380	Phase 2
0.8681	High Similarity	NPD1512	Approved
0.8671	High Similarity	NPD6799	Approved
0.8649	High Similarity	NPD7819	Suspended
0.8514	High Similarity	NPD7411	Suspended
0.8478	Intermediate Similarity	NPD943	Approved
0.8477	Intermediate Similarity	NPD7075	Discontinued
0.8467	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.8462	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.844	Intermediate Similarity	NPD1551	Phase 2
0.84	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.8357	Intermediate Similarity	NPD6651	Approved
0.8355	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.8344	Intermediate Similarity	NPD3817	Phase 2
0.8333	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.8333	Intermediate Similarity	NPD3750	Approved
0.8322	Intermediate Similarity	NPD6599	Discontinued
0.8269	Intermediate Similarity	NPD6166	Phase 2
0.8269	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.8269	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.8258	Intermediate Similarity	NPD6232	Discontinued
0.8239	Intermediate Similarity	NPD1509	Clinical (unspecified phase)
0.8231	Intermediate Similarity	NPD2532	Approved
0.8231	Intermediate Similarity	NPD2533	Approved
0.8231	Intermediate Similarity	NPD2534	Approved
0.8217	Intermediate Similarity	NPD7473	Discontinued
0.8212	Intermediate Similarity	NPD6801	Discontinued
0.8194	Intermediate Similarity	NPD6959	Discontinued
0.817	Intermediate Similarity	NPD7768	Phase 2
0.8165	Intermediate Similarity	NPD3818	Discontinued
0.8153	Intermediate Similarity	NPD7852	Clinical (unspecified phase)
0.8138	Intermediate Similarity	NPD2800	Approved
0.8138	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.8125	Intermediate Similarity	NPD2344	Approved
0.8117	Intermediate Similarity	NPD3749	Approved
0.8113	Intermediate Similarity	NPD7054	Approved
0.8102	Intermediate Similarity	NPD1203	Approved
0.8063	Intermediate Similarity	NPD7074	Phase 3
0.8063	Intermediate Similarity	NPD7472	Approved
0.8052	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.8043	Intermediate Similarity	NPD2798	Approved
0.8014	Intermediate Similarity	NPD2654	Approved
0.8014	Intermediate Similarity	NPD1243	Approved
0.8013	Intermediate Similarity	NPD5494	Approved
0.8012	Intermediate Similarity	NPD6797	Phase 2
0.8	Intermediate Similarity	NPD5403	Approved
0.8	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7987	Intermediate Similarity	NPD5402	Approved
0.7986	Intermediate Similarity	NPD2799	Discontinued
0.7986	Intermediate Similarity	NPD3748	Approved
0.7963	Intermediate Similarity	NPD7251	Discontinued
0.7931	Intermediate Similarity	NPD6099	Approved
0.7931	Intermediate Similarity	NPD6100	Approved
0.7929	Intermediate Similarity	NPD6832	Phase 2
0.7919	Intermediate Similarity	NPD7390	Discontinued
0.7914	Intermediate Similarity	NPD7808	Phase 3
0.7905	Intermediate Similarity	NPD2309	Approved
0.7902	Intermediate Similarity	NPD230	Phase 1
0.7901	Intermediate Similarity	NPD5953	Discontinued
0.7895	Intermediate Similarity	NPD9493	Approved
0.7888	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7883	Intermediate Similarity	NPD3972	Approved
0.7883	Intermediate Similarity	NPD9717	Approved
0.7881	Intermediate Similarity	NPD920	Approved
0.7867	Intermediate Similarity	NPD5401	Approved
0.7862	Intermediate Similarity	NPD3926	Phase 2
0.7862	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7853	Intermediate Similarity	NPD6559	Discontinued
0.7852	Intermediate Similarity	NPD643	Clinical (unspecified phase)
0.7838	Intermediate Similarity	NPD4628	Phase 3
0.7805	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD9545	Approved
0.7778	Intermediate Similarity	NPD3226	Approved
0.7778	Intermediate Similarity	NPD7286	Phase 2
0.7748	Intermediate Similarity	NPD642	Clinical (unspecified phase)
0.7722	Intermediate Similarity	NPD919	Approved
0.7718	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7714	Intermediate Similarity	NPD1470	Approved
0.7698	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7697	Intermediate Similarity	NPD4419	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD411	Approved
0.7692	Intermediate Similarity	NPD2313	Discontinued
0.7681	Intermediate Similarity	NPD422	Phase 1
0.7681	Intermediate Similarity	NPD1547	Clinical (unspecified phase)
0.7681	Intermediate Similarity	NPD1201	Approved
0.7676	Intermediate Similarity	NPD4908	Phase 1
0.7669	Intermediate Similarity	NPD5844	Phase 1
0.7655	Intermediate Similarity	NPD447	Suspended
0.7647	Intermediate Similarity	NPD1548	Phase 1
0.7635	Intermediate Similarity	NPD2346	Discontinued
0.7626	Intermediate Similarity	NPD1608	Approved
0.7625	Intermediate Similarity	NPD1247	Approved
0.7622	Intermediate Similarity	NPD3027	Phase 3
0.7606	Intermediate Similarity	NPD9494	Approved
0.758	Intermediate Similarity	NPD1465	Phase 2
0.7578	Intermediate Similarity	NPD5710	Approved
0.7578	Intermediate Similarity	NPD5711	Approved
0.7576	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7569	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7569	Intermediate Similarity	NPD3268	Approved
0.7568	Intermediate Similarity	NPD5404	Approved
0.7568	Intermediate Similarity	NPD5408	Approved
0.7568	Intermediate Similarity	NPD5406	Approved
0.7568	Intermediate Similarity	NPD5405	Approved
0.7566	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7554	Intermediate Similarity	NPD1610	Phase 2
0.7518	Intermediate Similarity	NPD1876	Approved
0.75	Intermediate Similarity	NPD7033	Discontinued
0.75	Intermediate Similarity	NPD4308	Phase 3
0.75	Intermediate Similarity	NPD405	Clinical (unspecified phase)
0.7465	Intermediate Similarity	NPD2797	Approved
0.7465	Intermediate Similarity	NPD1164	Approved
0.7448	Intermediate Similarity	NPD3764	Approved
0.7445	Intermediate Similarity	NPD5536	Phase 2
0.7436	Intermediate Similarity	NPD7458	Discontinued
0.7431	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7415	Intermediate Similarity	NPD1933	Approved
0.741	Intermediate Similarity	NPD17	Approved
0.7407	Intermediate Similarity	NPD1241	Discontinued
0.7403	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7394	Intermediate Similarity	NPD3225	Approved
0.7379	Intermediate Similarity	NPD4625	Phase 3
0.7376	Intermediate Similarity	NPD9269	Phase 2
0.7368	Intermediate Similarity	NPD7003	Approved
0.7361	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7361	Intermediate Similarity	NPD3018	Phase 2
0.7347	Intermediate Similarity	NPD1613	Approved
0.7347	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7341	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7338	Intermediate Similarity	NPD4357	Discontinued
0.7338	Intermediate Similarity	NPD9268	Approved
0.7338	Intermediate Similarity	NPD1651	Approved
0.7329	Intermediate Similarity	NPD6971	Discontinued
0.7324	Intermediate Similarity	NPD4749	Approved
0.7312	Intermediate Similarity	NPD4288	Approved
0.7312	Intermediate Similarity	NPD2296	Approved
0.7305	Intermediate Similarity	NPD1729	Discontinued
0.7296	Intermediate Similarity	NPD6844	Discontinued
0.7293	Intermediate Similarity	NPD74	Approved
0.7293	Intermediate Similarity	NPD9266	Approved
0.7292	Intermediate Similarity	NPD1019	Discontinued
0.7289	Intermediate Similarity	NPD3751	Discontinued
0.7285	Intermediate Similarity	NPD1471	Phase 3
0.7273	Intermediate Similarity	NPD1283	Approved
0.7257	Intermediate Similarity	NPD4363	Phase 3
0.7257	Intermediate Similarity	NPD4360	Phase 2
0.7247	Intermediate Similarity	NPD7501	Clinical (unspecified phase)
0.723	Intermediate Similarity	NPD4307	Phase 2
0.7222	Intermediate Similarity	NPD3267	Approved
0.7222	Intermediate Similarity	NPD3266	Approved
0.7219	Intermediate Similarity	NPD6104	Discontinued
0.7218	Intermediate Similarity	NPD9265	Clinical (unspecified phase)
0.7218	Intermediate Similarity	NPD9264	Approved
0.7218	Intermediate Similarity	NPD9267	Approved
0.7218	Intermediate Similarity	NPD9263	Approved
0.7216	Intermediate Similarity	NPD4361	Phase 2
0.7216	Intermediate Similarity	NPD4362	Clinical (unspecified phase)
0.7215	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7214	Intermediate Similarity	NPD4196	Clinical (unspecified phase)
0.7212	Intermediate Similarity	NPD5242	Approved
0.7211	Intermediate Similarity	NPD1296	Phase 2
0.7208	Intermediate Similarity	NPD6190	Approved
0.7203	Intermediate Similarity	NPD2982	Phase 2
0.7203	Intermediate Similarity	NPD2983	Phase 2
0.7203	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7195	Intermediate Similarity	NPD7199	Phase 2
0.7188	Intermediate Similarity	NPD37	Approved
0.7175	Intermediate Similarity	NPD8090	Clinical (unspecified phase)
0.7172	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD1778	Approved
0.7163	Intermediate Similarity	NPD4626	Approved
0.7154	Intermediate Similarity	NPD1242	Phase 1
0.7152	Intermediate Similarity	NPD7229	Phase 3
0.7152	Intermediate Similarity	NPD3787	Discontinued
0.7133	Intermediate Similarity	NPD2981	Phase 2
0.7133	Intermediate Similarity	NPD1481	Phase 2
0.7126	Intermediate Similarity	NPD4287	Approved
0.7126	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7125	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7125	Intermediate Similarity	NPD6386	Approved
0.7125	Intermediate Similarity	NPD6385	Approved
0.7123	Intermediate Similarity	NPD2861	Phase 2
0.7118	Intermediate Similarity	NPD3658	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