NPASS Compound

Structure

CID314682 OpenBabel06191716122D 24 26 0 0 1 0 0 0 0 0999 V2000 -2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -3.0000 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 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -3.0000 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 -4.3301 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 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 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -3.0000 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 -1.7321 -2.0000 0.0000 C 0 0 3 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 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 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 24 1 0 0 0 0 5 7 1 0 0 0 0 5 14 2 0 0 0 0 6 8 2 0 0 0 0 6 14 1 0 0 0 0 7 16 2 0 0 0 0 8 16 1 0 0 0 0 9 10 1 0 0 0 0 9 15 1 0 0 0 0 10 21 1 0 0 0 0 11 14 1 0 0 0 0 11 18 1 0 0 0 0 12 15 2 0 0 0 0 12 19 1 0 0 0 0 13 17 2 0 0 0 0 13 20 1 0 0 0 0 15 17 1 0 0 0 0 16 22 1 0 0 0 0 17 18 1 0 0 0 0 18 21 1 0 0 0 0 19 20 2 0 0 0 0 19 23 1 0 0 0 0 20 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	327.18
Volume:	350.355
LogP:	3.085
LogD:	3.209
LogS:	-2.852
# Rotatable Bonds:	5
TPSA:	30.93
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.841
Synthetic Accessibility Score:	2.488
Fsp3:	0.4
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:	-4.577
MDCK Permeability:	2.3645903638680466e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.815
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.624
30% Bioavailability (F30%):	0.808

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.99
Plasma Protein Binding (PPB):	76.20730590820312%
Volume Distribution (VD):	2.053
Pgp-substrate:	7.783967018127441%

ADMET: Metabolism

CYP1A2-inhibitor:	0.173
CYP1A2-substrate:	0.975
CYP2C19-inhibitor:	0.289
CYP2C19-substrate:	0.967
CYP2C9-inhibitor:	0.022
CYP2C9-substrate:	0.721
CYP2D6-inhibitor:	0.757
CYP2D6-substrate:	0.952
CYP3A4-inhibitor:	0.089
CYP3A4-substrate:	0.929

ADMET: Excretion

Clearance (CL):	11.059
Half-life (T1/2):	0.602

ADMET: Toxicity

hERG Blockers:	0.948
Human Hepatotoxicity (H-HT):	0.201
Drug-inuced Liver Injury (DILI):	0.478
AMES Toxicity:	0.273
Rat Oral Acute Toxicity:	0.687
Maximum Recommended Daily Dose:	0.902
Skin Sensitization:	0.376
Carcinogencity:	0.064
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.925

Download Data

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

Natural Product: NPC314682

Natural Product ID:	NPC314682
*Common Name:**	6,7-Dimethoxy-1-[(4-Methoxyphenyl)Methyl]-2-Methyl-3,4-Dihydro-1H-Isoquinoline
IUPAC Name:	6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1H-isoquinoline
Synonyms:	7,12-O,O'-dimethyl-N-methylcoclaurine
Standard InCHIKey:	LZJWNVLTWYMMDJ-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H25NO3/c1-21-10-9-15-12-19(23-3)20(24-4)13-17(15)18(21)11-14-5-7-16(22-2)8-6-14/h5-8,12-13,18H,9-11H2,1-4H3
SMILES:	COc1ccc(cc1)CC1N(C)CCc2c1cc(OC)c(c2)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL452500
PubChem CID:	259676
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

*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
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075784]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	stem	n.a.	PMID[10096848]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	root	n.a.	PMID[10096848]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	root and stem	n.a.	n.a.	PMID[10096848]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11473438]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	root	n.a.	PMID[20030508]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[20593839]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[21214233]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21214233]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3728032]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[8281582]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[8289066]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[8450318]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9917283]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17299	Stephania discolor	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29079	Radix stephaniae tetrandrae	Species	Lymnaeidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22932	Anser cygnoides domestica	Species	Anatidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17299	Stephania discolor	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5493	Rhizoma menispermi	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO14376	Stephania cephalantha	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13978	Cissampelos pareira	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17299	Stephania discolor	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18410	Cyclea racemosa	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20526	Menispermum dauricum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13978	Cissampelos pareira	Species	Menispermaceae	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	2
Ki	2

Activity Type	# Activity
Protein Family	2
Tissue	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT968	Protein Family	Adrenergic receptor alpha-1	Rattus norvegicus	Ki	=	7943.28	nM	PMID[549726]
NPT2685	Protein Family	Voltage-gated L-type calcium channel	Rattus norvegicus	Ki	=	4168.69	nM	PMID[549726]
NPT177	Tissue	Aorta	Rattus norvegicus	IC50	=	66069.34	nM	PMID[549726]
NPT177	Tissue	Aorta	Rattus norvegicus	IC50	=	14791.08	nM	PMID[549726]

☑ 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 NPC314682 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	300
0.1-0.2	1647
0.2-0.3	10006
0.3-0.4	7706
0.4-0.5	7205
0.5-0.6	11538
0.6-0.7	3252
0.7-0.8	659
0.8-0.85	210
0.85-0.9	120
0.9-0.95	46
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
0.9924	High Similarity	NPC213206
0.9924	High Similarity	NPC474915
0.9924	High Similarity	NPC188163
0.9924	High Similarity	NPC328750
0.9632	High Similarity	NPC185838
0.963	High Similarity	NPC128019
0.963	High Similarity	NPC136860
0.963	High Similarity	NPC476567
0.9493	High Similarity	NPC321505
0.9493	High Similarity	NPC51957
0.9493	High Similarity	NPC179825
0.9493	High Similarity	NPC210437
0.9493	High Similarity	NPC191376
0.9493	High Similarity	NPC106295
0.9493	High Similarity	NPC16107
0.9493	High Similarity	NPC476144
0.9424	High Similarity	NPC475959
0.9424	High Similarity	NPC135538
0.9424	High Similarity	NPC24233
0.9424	High Similarity	NPC147390
0.9424	High Similarity	NPC246587
0.9424	High Similarity	NPC428
0.9424	High Similarity	NPC7467
0.9424	High Similarity	NPC476571
0.9353	High Similarity	NPC476151
0.9313	High Similarity	NPC160193
0.9225	High Similarity	NPC81733
0.9225	High Similarity	NPC326316
0.922	High Similarity	NPC477565
0.922	High Similarity	NPC103379
0.922	High Similarity	NPC60538
0.922	High Similarity	NPC207824
0.9209	High Similarity	NPC130926
0.916	High Similarity	NPC172403
0.9155	High Similarity	NPC151895
0.9155	High Similarity	NPC97221
0.9155	High Similarity	NPC192768
0.9155	High Similarity	NPC220858
0.9155	High Similarity	NPC88249
0.9118	High Similarity	NPC253429
0.9091	High Similarity	NPC277669
0.9091	High Similarity	NPC476568
0.9091	High Similarity	NPC76213
0.9085	High Similarity	NPC219162
0.9085	High Similarity	NPC92541
0.9034	High Similarity	NPC276588
0.9034	High Similarity	NPC110416
0.9034	High Similarity	NPC207757
0.9034	High Similarity	NPC204828
0.9034	High Similarity	NPC295691
0.9034	High Similarity	NPC41178
0.9034	High Similarity	NPC5238
0.9034	High Similarity	NPC39701
0.9034	High Similarity	NPC172765
0.9034	High Similarity	NPC138487
0.9034	High Similarity	NPC189266
0.9034	High Similarity	NPC278799
0.9034	High Similarity	NPC54379
0.9034	High Similarity	NPC127674
0.9034	High Similarity	NPC2413
0.9034	High Similarity	NPC184026
0.9034	High Similarity	NPC216459
0.9034	High Similarity	NPC469817
0.9034	High Similarity	NPC249797
0.9034	High Similarity	NPC193949
0.9028	High Similarity	NPC233029
0.9028	High Similarity	NPC210148
0.8973	High Similarity	NPC247639
0.8973	High Similarity	NPC25084
0.8973	High Similarity	NPC146288
0.8944	High Similarity	NPC144863
0.8944	High Similarity	NPC90844
0.8944	High Similarity	NPC253883
0.8944	High Similarity	NPC95075
0.8912	High Similarity	NPC476572
0.8904	High Similarity	NPC187022
0.8904	High Similarity	NPC325871
0.8904	High Similarity	NPC80129
0.8904	High Similarity	NPC99659
0.8889	High Similarity	NPC274026
0.8881	High Similarity	NPC130941
0.8844	High Similarity	NPC203784
0.8844	High Similarity	NPC234392
0.8844	High Similarity	NPC170503
0.8844	High Similarity	NPC126519
0.8844	High Similarity	NPC31311
0.8836	High Similarity	NPC477564
0.8836	High Similarity	NPC2295
0.8832	High Similarity	NPC11147
0.8828	High Similarity	NPC476579
0.8824	High Similarity	NPC160692
0.8792	High Similarity	NPC306902
0.8792	High Similarity	NPC166014
0.8792	High Similarity	NPC27410
0.8792	High Similarity	NPC160298
0.8792	High Similarity	NPC232924
0.8792	High Similarity	NPC477559
0.8792	High Similarity	NPC266753
0.8786	High Similarity	NPC470925
0.8776	High Similarity	NPC78733
0.8768	High Similarity	NPC301050
0.8768	High Similarity	NPC131204
0.8768	High Similarity	NPC7018
0.8767	High Similarity	NPC82285
0.8767	High Similarity	NPC133011
0.8767	High Similarity	NPC148898
0.875	High Similarity	NPC118419
0.8725	High Similarity	NPC477080
0.8725	High Similarity	NPC111485
0.8725	High Similarity	NPC216816
0.8716	High Similarity	NPC147091
0.8675	High Similarity	NPC475393
0.8649	High Similarity	NPC93593
0.8649	High Similarity	NPC244112
0.8639	High Similarity	NPC470924
0.8639	High Similarity	NPC26601
0.8618	High Similarity	NPC276944
0.8618	High Similarity	NPC225774
0.8618	High Similarity	NPC238530
0.8618	High Similarity	NPC232514
0.8601	High Similarity	NPC294249
0.86	High Similarity	NPC118804
0.8562	High Similarity	NPC240841
0.8562	High Similarity	NPC42549
0.8562	High Similarity	NPC476432
0.8562	High Similarity	NPC317272
0.8562	High Similarity	NPC219341
0.8562	High Similarity	NPC13916
0.8562	High Similarity	NPC256012
0.8562	High Similarity	NPC250846
0.8562	High Similarity	NPC264850
0.8562	High Similarity	NPC268503
0.8562	High Similarity	NPC24264
0.8553	High Similarity	NPC233650
0.8553	High Similarity	NPC324144
0.8523	High Similarity	NPC76079
0.8514	High Similarity	NPC37272
0.8506	High Similarity	NPC81218
0.8506	High Similarity	NPC145832
0.8506	High Similarity	NPC247389
0.8506	High Similarity	NPC12053
0.8506	High Similarity	NPC117188
0.8506	High Similarity	NPC205421
0.8506	High Similarity	NPC474931
0.8506	High Similarity	NPC306555
0.8506	High Similarity	NPC158376
0.8506	High Similarity	NPC298979
0.8503	High Similarity	NPC223125
0.8497	Intermediate Similarity	NPC96603
0.8497	Intermediate Similarity	NPC284183
0.8497	Intermediate Similarity	NPC24465
0.8497	Intermediate Similarity	NPC134858
0.8497	Intermediate Similarity	NPC477563
0.8497	Intermediate Similarity	NPC4138
0.8497	Intermediate Similarity	NPC302527
0.8497	Intermediate Similarity	NPC121275
0.8497	Intermediate Similarity	NPC136508
0.8497	Intermediate Similarity	NPC78222
0.8497	Intermediate Similarity	NPC212794
0.8497	Intermediate Similarity	NPC13504
0.8497	Intermediate Similarity	NPC306843
0.8497	Intermediate Similarity	NPC16805
0.8497	Intermediate Similarity	NPC167546
0.8497	Intermediate Similarity	NPC196447
0.8497	Intermediate Similarity	NPC253043
0.8477	Intermediate Similarity	NPC59028
0.8477	Intermediate Similarity	NPC92191
0.8467	Intermediate Similarity	NPC323443
0.8467	Intermediate Similarity	NPC180756
0.8467	Intermediate Similarity	NPC186063
0.8452	Intermediate Similarity	NPC83198
0.8452	Intermediate Similarity	NPC204908
0.8452	Intermediate Similarity	NPC241055
0.8446	Intermediate Similarity	NPC8337
0.8446	Intermediate Similarity	NPC85747
0.8442	Intermediate Similarity	NPC476573
0.8442	Intermediate Similarity	NPC35627
0.8442	Intermediate Similarity	NPC81247
0.8442	Intermediate Similarity	NPC304659
0.8442	Intermediate Similarity	NPC86144
0.844	Intermediate Similarity	NPC193528
0.8431	Intermediate Similarity	NPC1229
0.8421	Intermediate Similarity	NPC249274
0.8421	Intermediate Similarity	NPC97072
0.8421	Intermediate Similarity	NPC215829
0.8421	Intermediate Similarity	NPC205167
0.8389	Intermediate Similarity	NPC223124
0.8389	Intermediate Similarity	NPC476580
0.8387	Intermediate Similarity	NPC210140
0.8387	Intermediate Similarity	NPC150879
0.8387	Intermediate Similarity	NPC210918
0.8377	Intermediate Similarity	NPC168409
0.8369	Intermediate Similarity	NPC167944
0.8369	Intermediate Similarity	NPC42793
0.8369	Intermediate Similarity	NPC231884
0.8366	Intermediate Similarity	NPC60186
0.8366	Intermediate Similarity	NPC24954
0.8355	Intermediate Similarity	NPC106786
0.8344	Intermediate Similarity	NPC227060
0.8344	Intermediate Similarity	NPC76682

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 NPC314682 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	205
0.1-0.2	767
0.2-0.3	1021
0.3-0.4	1598
0.4-0.5	2708
0.5-0.6	1849
0.6-0.7	733
0.7-0.8	223
0.8-0.85	29
0.85-0.9	14
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9924	High Similarity	NPD4664	Clinical (unspecified phase)
0.9493	High Similarity	NPD4584	Approved
0.9225	High Similarity	NPD4017	Approved
0.8951	High Similarity	NPD3641	Approved
0.8951	High Similarity	NPD3640	Phase 3
0.8951	High Similarity	NPD3639	Approved
0.8904	High Similarity	NPD7298	Approved
0.8819	High Similarity	NPD6030	Approved
0.8819	High Similarity	NPD6031	Approved
0.8815	High Similarity	NPD5718	Phase 2
0.8741	High Similarity	NPD2669	Clinical (unspecified phase)
0.8707	High Similarity	NPD4772	Phase 2
0.8707	High Similarity	NPD4773	Phase 2
0.8675	High Similarity	NPD7201	Clinical (unspecified phase)
0.8601	High Similarity	NPD5241	Discontinued
0.8571	High Similarity	NPD6029	Clinical (unspecified phase)
0.8571	High Similarity	NPD6028	Clinical (unspecified phase)
0.8529	High Similarity	NPD5752	Clinical (unspecified phase)
0.8442	Intermediate Similarity	NPD4010	Discontinued
0.8369	Intermediate Similarity	NPD6896	Approved
0.8369	Intermediate Similarity	NPD6895	Approved
0.8356	Intermediate Similarity	NPD3124	Discontinued
0.8355	Intermediate Similarity	NPD6788	Approved
0.8344	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.8344	Intermediate Similarity	NPD8252	Approved
0.8344	Intermediate Similarity	NPD8099	Discontinued
0.8344	Intermediate Similarity	NPD8251	Approved
0.8291	Intermediate Similarity	NPD8156	Discontinued
0.8258	Intermediate Similarity	NPD6107	Approved
0.8258	Intermediate Similarity	NPD7802	Discontinued
0.8219	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.8217	Intermediate Similarity	NPD2898	Approved
0.8205	Intermediate Similarity	NPD4166	Phase 2
0.82	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.8182	Intermediate Similarity	NPD7831	Phase 2
0.8182	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.8182	Intermediate Similarity	NPD7833	Phase 2
0.817	Intermediate Similarity	NPD5977	Approved
0.817	Intermediate Similarity	NPD5978	Approved
0.8165	Intermediate Similarity	NPD5602	Clinical (unspecified phase)
0.8163	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.8156	Intermediate Similarity	NPD3109	Approved
0.8156	Intermediate Similarity	NPD3110	Approved
0.8095	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.8085	Intermediate Similarity	NPD4475	Approved
0.8085	Intermediate Similarity	NPD4474	Approved
0.8075	Intermediate Similarity	NPD6297	Approved
0.8054	Intermediate Similarity	NPD1754	Clinical (unspecified phase)
0.7988	Intermediate Similarity	NPD8054	Approved
0.7988	Intermediate Similarity	NPD8053	Approved
0.7987	Intermediate Similarity	NPD2420	Approved
0.7987	Intermediate Similarity	NPD2421	Approved
0.7975	Intermediate Similarity	NPD3051	Approved
0.7975	Intermediate Similarity	NPD6071	Discontinued
0.7974	Intermediate Similarity	NPD7110	Phase 1
0.7974	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.7959	Intermediate Similarity	NPD5177	Phase 3
0.795	Intermediate Similarity	NPD5313	Approved
0.795	Intermediate Similarity	NPD5312	Approved
0.7935	Intermediate Similarity	NPD2560	Approved
0.7935	Intermediate Similarity	NPD2563	Approved
0.7933	Intermediate Similarity	NPD1424	Approved
0.7925	Intermediate Similarity	NPD2969	Approved
0.7925	Intermediate Similarity	NPD2970	Approved
0.7919	Intermediate Similarity	NPD3845	Phase 1
0.7919	Intermediate Similarity	NPD7124	Phase 2
0.7905	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7879	Intermediate Similarity	NPD6853	Approved
0.7879	Intermediate Similarity	NPD6851	Approved
0.7875	Intermediate Similarity	NPD27	Approved
0.7875	Intermediate Similarity	NPD4481	Phase 3
0.7875	Intermediate Similarity	NPD2489	Approved
0.7857	Intermediate Similarity	NPD7905	Discontinued
0.7842	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7832	Intermediate Similarity	NPD554	Clinical (unspecified phase)
0.7832	Intermediate Similarity	NPD2674	Phase 3
0.7829	Intermediate Similarity	NPD6662	Clinical (unspecified phase)
0.7812	Intermediate Similarity	NPD6687	Approved
0.7812	Intermediate Similarity	NPD6688	Approved
0.78	Intermediate Similarity	NPD2422	Clinical (unspecified phase)
0.7786	Intermediate Similarity	NPD4098	Discontinued
0.7785	Intermediate Similarity	NPD6748	Discontinued
0.7785	Intermediate Similarity	NPD3977	Clinical (unspecified phase)
0.7763	Intermediate Similarity	NPD3647	Clinical (unspecified phase)
0.7744	Intermediate Similarity	NPD5283	Phase 1
0.7738	Intermediate Similarity	NPD7291	Discontinued
0.7737	Intermediate Similarity	NPD2667	Approved
0.7737	Intermediate Similarity	NPD2668	Approved
0.7722	Intermediate Similarity	NPD4055	Discovery
0.7718	Intermediate Similarity	NPD3060	Approved
0.7718	Intermediate Similarity	NPD4162	Approved
0.7711	Intermediate Similarity	NPD5917	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD5720	Discontinued
0.7687	Intermediate Similarity	NPD1753	Discontinued
0.7683	Intermediate Similarity	NPD3920	Phase 2
0.7677	Intermediate Similarity	NPD6876	Approved
0.7677	Intermediate Similarity	NPD6875	Approved
0.7671	Intermediate Similarity	NPD4579	Clinical (unspecified phase)
0.7643	Intermediate Similarity	NPD1420	Approved
0.7643	Intermediate Similarity	NPD1421	Approved
0.7643	Intermediate Similarity	NPD1669	Approved
0.7639	Intermediate Similarity	NPD3145	Approved
0.7639	Intermediate Similarity	NPD3144	Approved
0.7639	Intermediate Similarity	NPD6812	Clinical (unspecified phase)
0.7635	Intermediate Similarity	NPD1632	Clinical (unspecified phase)
0.7632	Intermediate Similarity	NPD7598	Phase 2
0.7625	Intermediate Similarity	NPD5677	Discontinued
0.7613	Intermediate Similarity	NPD4005	Discontinued
0.76	Intermediate Similarity	NPD4237	Approved
0.76	Intermediate Similarity	NPD4236	Phase 3
0.7586	Intermediate Similarity	NPD3530	Approved
0.7586	Intermediate Similarity	NPD3531	Approved
0.7586	Intermediate Similarity	NPD3532	Approved
0.7572	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7571	Intermediate Similarity	NPD2233	Approved
0.7571	Intermediate Similarity	NPD2232	Approved
0.7571	Intermediate Similarity	NPD2230	Approved
0.7564	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.7561	Intermediate Similarity	NPD5708	Clinical (unspecified phase)
0.756	Intermediate Similarity	NPD6618	Phase 2
0.7551	Intermediate Similarity	NPD2989	Phase 2
0.7551	Intermediate Similarity	NPD2986	Phase 2
0.7551	Intermediate Similarity	NPD2492	Phase 1
0.755	Intermediate Similarity	NPD6331	Phase 2
0.755	Intermediate Similarity	NPD5754	Discontinued
0.7547	Intermediate Similarity	NPD4581	Clinical (unspecified phase)
0.7536	Intermediate Similarity	NPD2595	Approved
0.7536	Intermediate Similarity	NPD2594	Approved
0.7533	Intermediate Similarity	NPD7045	Clinical (unspecified phase)
0.7517	Intermediate Similarity	NPD5111	Phase 2
0.7517	Intermediate Similarity	NPD5109	Approved
0.7517	Intermediate Similarity	NPD5110	Phase 2
0.7515	Intermediate Similarity	NPD5087	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2971	Approved
0.75	Intermediate Similarity	NPD3692	Discontinued
0.75	Intermediate Similarity	NPD3924	Approved
0.75	Intermediate Similarity	NPD2968	Approved
0.75	Intermediate Similarity	NPD6111	Discontinued
0.75	Intermediate Similarity	NPD7281	Phase 3
0.75	Intermediate Similarity	NPD3922	Approved
0.75	Intermediate Similarity	NPD3923	Approved
0.75	Intermediate Similarity	NPD7280	Phase 3
0.75	Intermediate Similarity	NPD3921	Approved
0.7486	Intermediate Similarity	NPD4420	Approved
0.7484	Intermediate Similarity	NPD5976	Discontinued
0.7483	Intermediate Similarity	NPD6364	Approved
0.7483	Intermediate Similarity	NPD44	Approved
0.7468	Intermediate Similarity	NPD4123	Phase 3
0.7451	Intermediate Similarity	NPD2120	Phase 2
0.7443	Intermediate Similarity	NPD8095	Phase 1
0.7432	Intermediate Similarity	NPD2653	Approved
0.7431	Intermediate Similarity	NPD3637	Approved
0.7431	Intermediate Similarity	NPD3636	Approved
0.7431	Intermediate Similarity	NPD3635	Approved
0.7427	Intermediate Similarity	NPD7906	Approved
0.7425	Intermediate Similarity	NPD6996	Clinical (unspecified phase)
0.7421	Intermediate Similarity	NPD2978	Approved
0.7421	Intermediate Similarity	NPD2977	Approved
0.7417	Intermediate Similarity	NPD7153	Discontinued
0.7415	Intermediate Similarity	NPD2238	Phase 2
0.7413	Intermediate Similarity	NPD3053	Approved
0.7413	Intermediate Similarity	NPD3055	Approved
0.741	Intermediate Similarity	NPD4093	Discontinued
0.741	Intermediate Similarity	NPD3443	Approved
0.741	Intermediate Similarity	NPD6382	Discontinued
0.741	Intermediate Similarity	NPD3444	Approved
0.741	Intermediate Similarity	NPD3445	Approved
0.7405	Intermediate Similarity	NPD6385	Approved
0.7405	Intermediate Similarity	NPD6386	Approved
0.74	Intermediate Similarity	NPD2161	Phase 2
0.7396	Intermediate Similarity	NPD7311	Approved
0.7396	Intermediate Similarity	NPD7312	Approved
0.7396	Intermediate Similarity	NPD7313	Approved
0.7396	Intermediate Similarity	NPD4578	Approved
0.7396	Intermediate Similarity	NPD4577	Approved
0.7396	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7396	Intermediate Similarity	NPD7310	Approved
0.7394	Intermediate Similarity	NPD5966	Clinical (unspecified phase)
0.7391	Intermediate Similarity	NPD5604	Discontinued
0.7389	Intermediate Similarity	NPD6357	Discontinued
0.7386	Intermediate Similarity	NPD3301	Approved
0.7386	Intermediate Similarity	NPD5160	Discontinued
0.7372	Intermediate Similarity	NPD4727	Phase 1
0.7372	Intermediate Similarity	NPD1914	Approved
0.7361	Intermediate Similarity	NPD2987	Approved
0.7361	Intermediate Similarity	NPD2990	Approved
0.7358	Intermediate Similarity	NPD7945	Clinical (unspecified phase)
0.7353	Intermediate Similarity	NPD7309	Approved
0.7351	Intermediate Similarity	NPD3656	Approved
0.7349	Intermediate Similarity	NPD4498	Clinical (unspecified phase)
0.7346	Intermediate Similarity	NPD7400	Phase 3
0.7341	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7338	Intermediate Similarity	NPD2486	Discontinued
0.7337	Intermediate Similarity	NPD7132	Clinical (unspecified phase)
0.733	Intermediate Similarity	NPD7034	Discontinued
0.7329	Intermediate Similarity	NPD5155	Approved
0.7329	Intermediate Similarity	NPD5156	Approved
0.7325	Intermediate Similarity	NPD2883	Discontinued
0.7325	Intermediate Similarity	NPD4210	Discontinued
0.7319	Intermediate Similarity	NPD3596	Phase 2

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