NPASS Compound

Structure

CID181138 OpenBabel06191715552D 27 31 0 0 1 0 0 0 0 0999 V2000 4.5002 4.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3662 -1.3820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9401 -0.5181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3523 -1.3271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5334 0.3955 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3578 -1.2226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3633 2.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 2.9271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7681 1.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7681 3.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3662 1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5002 3.1180 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6342 1.6180 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6342 2.6180 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5002 1.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5388 0.5000 0.0000 C 0 0 0 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 1.9021 1.6180 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5002 0.1180 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 0.9511 1.3090 0.0000 C 0 0 2 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 1.9021 2.6180 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 3.6342 -0.3820 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 1.5878 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3662 -0.3820 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3662 2.6180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 26 1 0 0 0 0 3 4 2 0 0 0 0 3 5 1 0 0 0 0 4 6 1 0 0 0 0 5 16 2 0 0 0 0 6 17 2 0 0 0 0 7 8 1 0 0 0 0 8 23 1 0 0 0 0 9 18 1 0 0 0 0 10 23 1 0 0 0 0 11 15 2 0 0 0 0 11 27 1 0 0 0 0 12 1 1 1 0 0 0 12 14 1 0 0 0 0 12 27 1 0 0 0 0 13 9 1 1 0 0 0 13 14 1 0 0 0 0 13 15 1 0 0 0 0 14 10 1 6 0 0 0 15 19 1 0 0 0 0 16 17 1 0 0 0 0 16 21 1 0 0 0 0 17 22 1 0 0 0 0 18 21 1 1 0 0 0 18 23 1 0 0 0 0 19 24 2 0 0 0 0 19 26 1 0 0 0 0 20 21 1 0 0 0 0 20 22 2 0 0 0 0 20 25 1 0 0 0 0 21 7 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	368.17
Volume:	370.326
LogP:	2.872
LogD:	2.815
LogS:	-3.075
# Rotatable Bonds:	2
TPSA:	67.87
# H-Bond Aceptor:	6
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.769
Synthetic Accessibility Score:	4.712
Fsp3:	0.524
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.83
MDCK Permeability:	2.909565228037536e-05
Pgp-inhibitor:	0.005
Pgp-substrate:	0.167
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.83
30% Bioavailability (F30%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.985
Plasma Protein Binding (PPB):	61.41642761230469%
Volume Distribution (VD):	1.49
Pgp-substrate:	48.81610107421875%

ADMET: Metabolism

CYP1A2-inhibitor:	0.215
CYP1A2-substrate:	0.665
CYP2C19-inhibitor:	0.511
CYP2C19-substrate:	0.928
CYP2C9-inhibitor:	0.616
CYP2C9-substrate:	0.115
CYP2D6-inhibitor:	0.886
CYP2D6-substrate:	0.651
CYP3A4-inhibitor:	0.915
CYP3A4-substrate:	0.92

ADMET: Excretion

Clearance (CL):	9.727
Half-life (T1/2):	0.357

ADMET: Toxicity

hERG Blockers:	0.414
Human Hepatotoxicity (H-HT):	0.51
Drug-inuced Liver Injury (DILI):	0.309
AMES Toxicity:	0.728
Rat Oral Acute Toxicity:	0.864
Maximum Recommended Daily Dose:	0.913
Skin Sensitization:	0.758
Carcinogencity:	0.962
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.969

Download Data

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

Natural Product: NPC181138

Natural Product ID:	NPC181138
*Common Name:**	Methyl (1R,4As,5As,6S,10Ar)-1-Methyl-2'-Oxospiro[1,4A,5,5A,7,8,10,10A-Octahydropyrano[3,4-F]Indolizine-6,3'-1H-Indole]-4-Carboxylate
IUPAC Name:	methyl (1R,4aS,5aS,6S,10aR)-1-methyl-2'-oxospiro[1,4a,5,5a,7,8,10,10a-octahydropyrano[3,4-f]indolizine-6,3'-1H-indole]-4-carboxylate
Synonyms:
Standard InCHIKey:	JMIAZDVHNCCPDM-DQDWJNSRSA-N
Standard InCHI:	InChI=1S/C21H24N2O4/c1-12-14-10-23-8-7-21(16-5-3-4-6-17(16)22-20(21)25)18(23)9-13(14)15(11-27-12)19(24)26-2/h3-6,11-14,18H,7-10H2,1-2H3,(H,22,25)/t12-,13+,14-,18+,21+/m1/s1
SMILES:	COC(=O)C1=CO[C@@H]([C@@H]2[C@@H]1C[C@@H]1N(C2)CC[C@]21C(=Nc1c2cccc1)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2355088
PubChem CID:	188999
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000251] Indolizidines

*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
NPO17943	Amburana cearensis	Species	Fabaceae	Eukaryota	n.a.	trunk bark	n.a.	DOI[10.1016/S0031-9422(98)00497-X]
NPO19381	Maxillaria densa	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10479332]
NPO26925	Fomitopsis pinicola	Species	Fomitopsidaceae	Eukaryota	n.a.	fruit body	n.a.	PMID[15679320]
NPO26925	Fomitopsis pinicola	Species	Fomitopsidaceae	Eukaryota	fruit bodies	Tokushima, Japan	1999-Autumn	PMID[15679320]
NPO9390	Uncaria gambir	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21192716]
NPO18193	Clivia nobilis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21469691]
NPO19381	Maxillaria densa	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23234371]
NPO22126	Penicillium funiculosum	Species	Trichocomaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27359163]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26925	Fomitopsis pinicola	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9390	Uncaria gambir	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9734	Vincetoxicum hirundinaria	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26925	Fomitopsis pinicola	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1603	Monostroma nitidum	Species	Monostromataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9390	Uncaria gambir	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27397	Drymaria cordata	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9390	Uncaria gambir	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19583	Ficus nervosa	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26795	Pityophthorus pityographus	Species	Curculionidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9734	Vincetoxicum hirundinaria	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27913	Ageratina tomentella	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18817	Platycarpha glomerata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO8745	Senecio alloeophyllus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28001	Zeora sordida	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4940	Peyrousea umbellata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO10315	Cestrum parqui	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17943	Amburana cearensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11596	Lomatia ilicifolia	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1603	Monostroma nitidum	Species	Monostromataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27246	Cercis chinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4468	Cuspidaria pterocarpa	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28120	Anisopappus pinnatifidus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19381	Maxillaria densa	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27221	Prosopis spicigera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9282	Stereocaulon colensoi	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18193	Clivia nobilis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO907	Dictyostelium purpureum	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18277	Scurrula fusca	Species	Loranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27397	Drymaria cordata	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26925	Fomitopsis pinicola	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27722	Caralluma stalagmifera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14694	Sickingia williamsii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO11476	Lecanora broccha	Species	Lecanoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9390	Uncaria gambir	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18862	Aria pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22126	Penicillium funiculosum	Species	Trichocomaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19160	Klasea quinquefolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10499	Haplopappus paucidentatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15198	Leproloma diffusum	Species	Stereocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6849	Lomatia arborescens	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28344	Rubus xanthocarpus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9061	Euthamia graminifolia	Species	Asteraceae	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
Potency	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT50	Individual Protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	20596.2	nM	PMID[509908]
NPT444	Individual Protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	28183.8	nM	PMID[509908]

☑ 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 NPC181138 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	193
0.1-0.2	894
0.2-0.3	2644
0.3-0.4	8660
0.4-0.5	20654
0.5-0.6	7893
0.6-0.7	1570
0.7-0.8	156
0.8-0.85	11
0.85-0.9	4
0.9-0.95	12
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC21752
1.0	High Similarity	NPC293255
1.0	High Similarity	NPC210415
1.0	High Similarity	NPC276993
1.0	High Similarity	NPC298851
0.9419	High Similarity	NPC148468
0.9419	High Similarity	NPC243673
0.9419	High Similarity	NPC63210
0.9419	High Similarity	NPC263709
0.9419	High Similarity	NPC310403
0.9419	High Similarity	NPC97380
0.9304	High Similarity	NPC52059
0.9304	High Similarity	NPC470069
0.9231	High Similarity	NPC153694
0.9231	High Similarity	NPC211525
0.9226	High Similarity	NPC161827
0.882	High Similarity	NPC472121
0.8302	Intermediate Similarity	NPC472100
0.8266	Intermediate Similarity	NPC475962
0.8125	Intermediate Similarity	NPC469460
0.8046	Intermediate Similarity	NPC99043
0.8046	Intermediate Similarity	NPC218594
0.7976	Intermediate Similarity	NPC474058
0.7966	Intermediate Similarity	NPC97584
0.7953	Intermediate Similarity	NPC469462
0.795	Intermediate Similarity	NPC472103
0.7931	Intermediate Similarity	NPC203202
0.7931	Intermediate Similarity	NPC264482
0.7895	Intermediate Similarity	NPC278887
0.7886	Intermediate Similarity	NPC186669
0.7861	Intermediate Similarity	NPC474077
0.7841	Intermediate Similarity	NPC6974
0.7821	Intermediate Similarity	NPC472209
0.7802	Intermediate Similarity	NPC28510
0.7709	Intermediate Similarity	NPC159963
0.768	Intermediate Similarity	NPC291759
0.7663	Intermediate Similarity	NPC204970
0.7637	Intermediate Similarity	NPC14994
0.7627	Intermediate Similarity	NPC476441
0.7624	Intermediate Similarity	NPC133591
0.7609	Intermediate Similarity	NPC25401
0.7582	Intermediate Similarity	NPC282092
0.7582	Intermediate Similarity	NPC38823
0.7582	Intermediate Similarity	NPC207033
0.7529	Intermediate Similarity	NPC473297
0.7527	Intermediate Similarity	NPC203972
0.7514	Intermediate Similarity	NPC472120
0.7514	Intermediate Similarity	NPC472101
0.7514	Intermediate Similarity	NPC472117
0.7514	Intermediate Similarity	NPC476425
0.75	Intermediate Similarity	NPC475559
0.75	Intermediate Similarity	NPC87714
0.7487	Intermediate Similarity	NPC1464
0.7486	Intermediate Similarity	NPC214960
0.7486	Intermediate Similarity	NPC279527
0.7474	Intermediate Similarity	NPC294909
0.7474	Intermediate Similarity	NPC128265
0.7474	Intermediate Similarity	NPC199851
0.7474	Intermediate Similarity	NPC254240
0.7474	Intermediate Similarity	NPC312870
0.7472	Intermediate Similarity	NPC13367
0.7461	Intermediate Similarity	NPC195787
0.7461	Intermediate Similarity	NPC246140
0.7459	Intermediate Similarity	NPC174629
0.7407	Intermediate Similarity	NPC302548
0.7399	Intermediate Similarity	NPC193410
0.7386	Intermediate Similarity	NPC472115
0.7386	Intermediate Similarity	NPC472114
0.7384	Intermediate Similarity	NPC477157
0.7384	Intermediate Similarity	NPC477156
0.7378	Intermediate Similarity	NPC243162
0.7377	Intermediate Similarity	NPC245741
0.7368	Intermediate Similarity	NPC478076
0.7366	Intermediate Similarity	NPC105055
0.7366	Intermediate Similarity	NPC22689
0.7363	Intermediate Similarity	NPC476428
0.7356	Intermediate Similarity	NPC248117
0.7356	Intermediate Similarity	NPC143457
0.7345	Intermediate Similarity	NPC167724
0.7345	Intermediate Similarity	NPC223595
0.7345	Intermediate Similarity	NPC224970
0.7341	Intermediate Similarity	NPC61013
0.733	Intermediate Similarity	NPC472106
0.7308	Intermediate Similarity	NPC39822
0.7299	Intermediate Similarity	NPC469461
0.7299	Intermediate Similarity	NPC36495
0.7283	Intermediate Similarity	NPC29285
0.7257	Intermediate Similarity	NPC309531
0.7257	Intermediate Similarity	NPC472102
0.7257	Intermediate Similarity	NPC225319
0.725	Intermediate Similarity	NPC189661
0.7241	Intermediate Similarity	NPC123241
0.7241	Intermediate Similarity	NPC113946
0.7216	Intermediate Similarity	NPC293458
0.7198	Intermediate Similarity	NPC476326
0.7194	Intermediate Similarity	NPC238457
0.7181	Intermediate Similarity	NPC5630
0.7152	Intermediate Similarity	NPC317758
0.7143	Intermediate Similarity	NPC203628
0.7135	Intermediate Similarity	NPC90967
0.7127	Intermediate Similarity	NPC96901
0.7119	Intermediate Similarity	NPC99632
0.7119	Intermediate Similarity	NPC282339
0.7113	Intermediate Similarity	NPC475489
0.7111	Intermediate Similarity	NPC469915
0.7098	Intermediate Similarity	NPC100863
0.7097	Intermediate Similarity	NPC258480
0.709	Intermediate Similarity	NPC473298
0.7088	Intermediate Similarity	NPC469726
0.7088	Intermediate Similarity	NPC329338
0.7077	Intermediate Similarity	NPC471512
0.7074	Intermediate Similarity	NPC181928
0.7074	Intermediate Similarity	NPC472323
0.7074	Intermediate Similarity	NPC21425
0.7062	Intermediate Similarity	NPC477158
0.7059	Intermediate Similarity	NPC52262
0.7059	Intermediate Similarity	NPC82070
0.7044	Intermediate Similarity	NPC234772
0.7037	Intermediate Similarity	NPC102338
0.7037	Intermediate Similarity	NPC63199
0.7037	Intermediate Similarity	NPC111602
0.7037	Intermediate Similarity	NPC196251
0.7037	Intermediate Similarity	NPC217294
0.7033	Intermediate Similarity	NPC214626
0.7033	Intermediate Similarity	NPC251212
0.7033	Intermediate Similarity	NPC139085
0.7022	Intermediate Similarity	NPC476231
0.7022	Intermediate Similarity	NPC176983
0.7019	Intermediate Similarity	NPC21638
0.701	Intermediate Similarity	NPC265642
0.701	Intermediate Similarity	NPC138615
0.701	Intermediate Similarity	NPC218733
0.701	Intermediate Similarity	NPC132874
0.6995	Remote Similarity	NPC303214
0.699	Remote Similarity	NPC232600
0.6981	Remote Similarity	NPC475720
0.6981	Remote Similarity	NPC474192
0.6976	Remote Similarity	NPC77777
0.6971	Remote Similarity	NPC475271
0.697	Remote Similarity	NPC14339
0.6968	Remote Similarity	NPC473007
0.6966	Remote Similarity	NPC201424
0.6963	Remote Similarity	NPC22476
0.6959	Remote Similarity	NPC116519
0.6957	Remote Similarity	NPC128476
0.6957	Remote Similarity	NPC129624
0.6952	Remote Similarity	NPC98197
0.6946	Remote Similarity	NPC221100
0.6946	Remote Similarity	NPC234078
0.6943	Remote Similarity	NPC34717
0.6942	Remote Similarity	NPC52254
0.6935	Remote Similarity	NPC15840
0.6931	Remote Similarity	NPC66210
0.6927	Remote Similarity	NPC286871
0.6923	Remote Similarity	NPC106593
0.6915	Remote Similarity	NPC472119
0.6911	Remote Similarity	NPC473008
0.6911	Remote Similarity	NPC472112
0.6908	Remote Similarity	NPC140311
0.6907	Remote Similarity	NPC245916
0.6905	Remote Similarity	NPC476436
0.6904	Remote Similarity	NPC469732
0.6898	Remote Similarity	NPC151171
0.6894	Remote Similarity	NPC325013
0.689	Remote Similarity	NPC473667
0.6889	Remote Similarity	NPC313757
0.6882	Remote Similarity	NPC321211
0.6878	Remote Similarity	NPC476114
0.6878	Remote Similarity	NPC322621
0.6872	Remote Similarity	NPC473458
0.6869	Remote Similarity	NPC473105
0.6866	Remote Similarity	NPC475816
0.6862	Remote Similarity	NPC477159
0.686	Remote Similarity	NPC37957
0.6857	Remote Similarity	NPC19175
0.6856	Remote Similarity	NPC221687
0.6856	Remote Similarity	NPC19692
0.6856	Remote Similarity	NPC220151
0.6851	Remote Similarity	NPC70172
0.685	Remote Similarity	NPC477161
0.6845	Remote Similarity	NPC281104
0.6845	Remote Similarity	NPC195636
0.6839	Remote Similarity	NPC242000
0.6839	Remote Similarity	NPC473004
0.6836	Remote Similarity	NPC114808
0.6831	Remote Similarity	NPC472118
0.6829	Remote Similarity	NPC69496
0.6828	Remote Similarity	NPC260075
0.6823	Remote Similarity	NPC474059
0.6821	Remote Similarity	NPC473375
0.6821	Remote Similarity	NPC97100
0.6816	Remote Similarity	NPC471122
0.6814	Remote Similarity	NPC127996
0.681	Remote Similarity	NPC478079
0.6806	Remote Similarity	NPC473815
0.6804	Remote Similarity	NPC470485
0.6802	Remote Similarity	NPC190945
0.6788	Remote Similarity	NPC472097
0.6782	Remote Similarity	NPC205926
0.6778	Remote Similarity	NPC315368

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 NPC181138 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	129
0.1-0.2	419
0.2-0.3	681
0.3-0.4	1111
0.4-0.5	3200
0.5-0.6	3107
0.6-0.7	494
0.7-0.8	9
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7474	Intermediate Similarity	NPD4500	Approved
0.7474	Intermediate Similarity	NPD4501	Approved
0.7168	Intermediate Similarity	NPD4121	Phase 3
0.7168	Intermediate Similarity	NPD4120	Approved
0.7126	Intermediate Similarity	NPD5741	Approved
0.7126	Intermediate Similarity	NPD5742	Approved
0.7126	Intermediate Similarity	NPD5743	Approved
0.7062	Intermediate Similarity	NPD7600	Phase 2
0.6984	Remote Similarity	NPD8103	Clinical (unspecified phase)
0.697	Remote Similarity	NPD5184	Approved
0.697	Remote Similarity	NPD5182	Approved
0.697	Remote Similarity	NPD5185	Approved
0.6919	Remote Similarity	NPD8006	Clinical (unspecified phase)
0.6888	Remote Similarity	NPD6874	Approved
0.686	Remote Similarity	NPD5595	Clinical (unspecified phase)
0.6851	Remote Similarity	NPD7591	Clinical (unspecified phase)
0.6845	Remote Similarity	NPD2569	Approved
0.6845	Remote Similarity	NPD2567	Approved
0.6829	Remote Similarity	NPD2613	Approved
0.6821	Remote Similarity	NPD4041	Approved
0.6816	Remote Similarity	NPD7599	Phase 2
0.6816	Remote Similarity	NPD7114	Clinical (unspecified phase)
0.6805	Remote Similarity	NPD3170	Approved
0.6802	Remote Similarity	NPD2435	Approved
0.6771	Remote Similarity	NPD6608	Clinical (unspecified phase)
0.676	Remote Similarity	NPD5715	Clinical (unspecified phase)
0.6758	Remote Similarity	NPD7036	Phase 3
0.6758	Remote Similarity	NPD7035	Approved
0.6751	Remote Similarity	NPD53	Approved
0.6751	Remote Similarity	NPD7777	Approved
0.6751	Remote Similarity	NPD7778	Approved
0.6739	Remote Similarity	NPD7795	Phase 2
0.6736	Remote Similarity	NPD4499	Approved
0.6723	Remote Similarity	NPD3399	Approved
0.6721	Remote Similarity	NPD8002	Clinical (unspecified phase)
0.6721	Remote Similarity	NPD8003	Clinical (unspecified phase)
0.6708	Remote Similarity	NPD2608	Approved
0.6708	Remote Similarity	NPD3132	Approved
0.6708	Remote Similarity	NPD4215	Approved
0.6708	Remote Similarity	NPD2609	Approved
0.6708	Remote Similarity	NPD3131	Approved
0.6708	Remote Similarity	NPD2611	Approved
0.6708	Remote Similarity	NPD4216	Approved
0.6708	Remote Similarity	NPD4218	Approved
0.6708	Remote Similarity	NPD2612	Approved
0.6708	Remote Similarity	NPD4217	Approved
0.6708	Remote Similarity	NPD2610	Approved
0.6707	Remote Similarity	NPD2566	Approved
0.6707	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD2571	Approved
0.6707	Remote Similarity	NPD3615	Approved
0.6707	Remote Similarity	NPD2570	Approved
0.6707	Remote Similarity	NPD3089	Approved
0.6707	Remote Similarity	NPD4745	Approved
0.6707	Remote Similarity	NPD3088	Approved
0.6707	Remote Similarity	NPD4746	Phase 3
0.6707	Remote Similarity	NPD3087	Approved
0.6707	Remote Similarity	NPD3090	Approved
0.6707	Remote Similarity	NPD2573	Approved
0.6707	Remote Similarity	NPD3614	Approved
0.6707	Remote Similarity	NPD2574	Discontinued
0.6707	Remote Similarity	NPD3616	Approved
0.6685	Remote Similarity	NPD2844	Phase 3
0.6685	Remote Similarity	NPD5811	Approved
0.6684	Remote Similarity	NPD4602	Approved
0.6684	Remote Similarity	NPD7252	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7569	Approved
0.6667	Remote Similarity	NPD7570	Approved
0.6667	Remote Similarity	NPD2994	Approved
0.6648	Remote Similarity	NPD7463	Clinical (unspecified phase)
0.6648	Remote Similarity	NPD4682	Phase 2
0.6647	Remote Similarity	NPD2670	Approved
0.6627	Remote Similarity	NPD4684	Phase 3
0.6627	Remote Similarity	NPD4685	Phase 3
0.6627	Remote Similarity	NPD4686	Approved
0.6625	Remote Similarity	NPD2212	Approved
0.6625	Remote Similarity	NPD2210	Approved
0.6617	Remote Similarity	NPD5721	Clinical (unspecified phase)
0.6617	Remote Similarity	NPD5848	Clinical (unspecified phase)
0.6604	Remote Similarity	NPD2117	Pre-registration
0.6604	Remote Similarity	NPD2115	Approved
0.6604	Remote Similarity	NPD2116	Approved
0.6601	Remote Similarity	NPD7174	Clinical (unspecified phase)
0.66	Remote Similarity	NPD4600	Approved
0.66	Remote Similarity	NPD4601	Approved
0.66	Remote Similarity	NPD6805	Discontinued
0.6593	Remote Similarity	NPD7244	Discontinued
0.6585	Remote Similarity	NPD5577	Clinical (unspecified phase)
0.6585	Remote Similarity	NPD5578	Approved
0.6584	Remote Similarity	NPD7205	Discontinued
0.6579	Remote Similarity	NPD6879	Phase 2
0.6579	Remote Similarity	NPD6878	Phase 2
0.6562	Remote Similarity	NPD3436	Approved
0.6561	Remote Similarity	NPD6641	Approved
0.6561	Remote Similarity	NPD6642	Approved
0.6561	Remote Similarity	NPD3965	Phase 1
0.6553	Remote Similarity	NPD4900	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD2820	Phase 3
0.6545	Remote Similarity	NPD7149	Clinical (unspecified phase)
0.6543	Remote Similarity	NPD3422	Phase 3
0.6543	Remote Similarity	NPD2946	Phase 2
0.6543	Remote Similarity	NPD3423	Phase 2
0.6536	Remote Similarity	NPD2948	Discontinued
0.6534	Remote Similarity	NPD6416	Phase 2
0.6531	Remote Similarity	NPD5077	Approved
0.6531	Remote Similarity	NPD5076	Approved
0.6522	Remote Similarity	NPD3031	Approved
0.6522	Remote Similarity	NPD3032	Approved
0.6522	Remote Similarity	NPD3030	Approved
0.6519	Remote Similarity	NPD6571	Approved
0.6519	Remote Similarity	NPD6570	Approved
0.6512	Remote Similarity	NPD1110	Approved
0.6512	Remote Similarity	NPD1109	Approved
0.65	Remote Similarity	NPD4987	Clinical (unspecified phase)
0.65	Remote Similarity	NPD6591	Clinical (unspecified phase)
0.6494	Remote Similarity	NPD2365	Approved
0.6492	Remote Similarity	NPD5899	Approved
0.6492	Remote Similarity	NPD5898	Approved
0.6492	Remote Similarity	NPD5897	Approved
0.649	Remote Similarity	NPD6657	Clinical (unspecified phase)
0.6485	Remote Similarity	NPD1036	Approved
0.6484	Remote Similarity	NPD3812	Clinical (unspecified phase)
0.648	Remote Similarity	NPD3329	Clinical (unspecified phase)
0.6477	Remote Similarity	NPD6017	Discontinued
0.6477	Remote Similarity	NPD7274	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD5186	Approved
0.6471	Remote Similarity	NPD5183	Approved
0.6468	Remote Similarity	NPD7810	Phase 3
0.6468	Remote Similarity	NPD7811	Phase 3
0.6468	Remote Similarity	NPD6661	Clinical (unspecified phase)
0.6468	Remote Similarity	NPD6999	Discontinued
0.6468	Remote Similarity	NPD7000	Clinical (unspecified phase)
0.6462	Remote Similarity	NPD6770	Approved
0.6458	Remote Similarity	NPD3435	Discontinued
0.645	Remote Similarity	NPD7238	Clinical (unspecified phase)
0.6445	Remote Similarity	NPD8325	Phase 3
0.6445	Remote Similarity	NPD8326	Phase 3
0.6445	Remote Similarity	NPD8327	Clinical (unspecified phase)
0.6441	Remote Similarity	NPD4607	Approved
0.6439	Remote Similarity	NPD7001	Phase 3
0.6439	Remote Similarity	NPD4901	Clinical (unspecified phase)
0.6439	Remote Similarity	NPD6732	Clinical (unspecified phase)
0.6436	Remote Similarity	NPD7687	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD6359	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD1663	Discontinued
0.6429	Remote Similarity	NPD4334	Discontinued
0.6425	Remote Similarity	NPD4506	Discontinued
0.6418	Remote Similarity	NPD4397	Phase 1
0.6417	Remote Similarity	NPD3984	Clinical (unspecified phase)
0.6417	Remote Similarity	NPD4986	Clinical (unspecified phase)
0.6417	Remote Similarity	NPD3983	Phase 3
0.6416	Remote Similarity	NPD6655	Clinical (unspecified phase)
0.6413	Remote Similarity	NPD2506	Approved
0.6404	Remote Similarity	NPD1801	Approved
0.6404	Remote Similarity	NPD3352	Approved
0.6404	Remote Similarity	NPD1802	Approved
0.64	Remote Similarity	NPD6414	Clinical (unspecified phase)
0.64	Remote Similarity	NPD2923	Approved
0.64	Remote Similarity	NPD3655	Clinical (unspecified phase)
0.6398	Remote Similarity	NPD4796	Discontinued
0.6393	Remote Similarity	NPD3589	Clinical (unspecified phase)
0.6384	Remote Similarity	NPD6185	Discontinued
0.6383	Remote Similarity	NPD3376	Clinical (unspecified phase)
0.6379	Remote Similarity	NPD4707	Clinical (unspecified phase)
0.6378	Remote Similarity	NPD6891	Phase 2
0.6378	Remote Similarity	NPD1742	Approved
0.6378	Remote Similarity	NPD1743	Approved
0.6378	Remote Similarity	NPD19	Approved
0.6374	Remote Similarity	NPD6309	Approved
0.6374	Remote Similarity	NPD6310	Approved
0.6374	Remote Similarity	NPD6311	Approved
0.6369	Remote Similarity	NPD979	Approved
0.6369	Remote Similarity	NPD7528	Approved
0.6369	Remote Similarity	NPD5881	Clinical (unspecified phase)
0.6368	Remote Similarity	NPD5466	Approved
0.6368	Remote Similarity	NPD5003	Discontinued
0.6368	Remote Similarity	NPD7940	Phase 3
0.6354	Remote Similarity	NPD5557	Phase 1
0.635	Remote Similarity	NPD7256	Discontinued
0.6349	Remote Similarity	NPD1165	Clinical (unspecified phase)
0.6347	Remote Similarity	NPD2160	Approved
0.6347	Remote Similarity	NPD2628	Approved
0.6347	Remote Similarity	NPD2627	Approved
0.6347	Remote Similarity	NPD2625	Approved
0.6347	Remote Similarity	NPD2626	Approved
0.6347	Remote Similarity	NPD2159	Approved
0.6344	Remote Similarity	NPD8008	Approved
0.6344	Remote Similarity	NPD8007	Approved
0.6343	Remote Similarity	NPD7702	Clinical (unspecified phase)
0.6343	Remote Similarity	NPD7820	Phase 3
0.634	Remote Similarity	NPD8658	Clinical (unspecified phase)
0.634	Remote Similarity	NPD8281	Discontinued
0.6339	Remote Similarity	NPD6396	Clinical (unspecified phase)
0.6339	Remote Similarity	NPD7105	Phase 1
0.6339	Remote Similarity	NPD6395	Phase 2
0.6335	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6335	Remote Similarity	NPD3909	Discontinued
0.6333	Remote Similarity	NPD4513	Discontinued
0.633	Remote Similarity	NPD6457	Approved
0.6329	Remote Similarity	NPD6296	Discontinued

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