NPASS Compound

Structure

CID153694 OpenBabel06191715522D 27 30 0 0 1 0 0 0 0 0999 V2000 5.8164 -1.8383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6203 -3.8383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9504 -2.3383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0214 -2.8052 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0269 -2.7007 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6092 -1.9962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3799 -1.7872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0159 0.7444 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0104 0.6399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3523 -1.8383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0844 -0.8383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3523 -3.8383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0844 -1.8383 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2183 -2.3383 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2183 -3.3383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -1.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2079 -0.9781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3523 -0.8383 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0844 -3.8383 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 1.6092 -0.1691 0.0000 C 0 0 1 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 3.2183 -0.3383 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 4.0844 -4.8383 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9504 -3.3383 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9706 1.4945 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4863 -3.3383 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 2 0 0 0 0 2 27 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 16 2 0 0 0 0 7 17 2 0 0 0 0 8 9 1 0 0 0 0 9 23 1 0 0 0 0 10 14 1 0 0 0 0 10 18 1 0 0 0 0 11 13 1 0 0 0 0 11 23 1 0 0 0 0 12 15 2 0 0 0 0 12 27 1 0 0 0 0 13 3 1 1 0 0 0 13 14 1 0 0 0 0 14 15 1 1 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 25 1 0 0 0 0 20 21 1 0 0 0 0 20 22 2 0 0 0 0 20 26 1 0 0 0 0 21 8 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	368.17
Volume:	376.246
LogP:	2.155
LogD:	1.686
LogS:	-2.974
# Rotatable Bonds:	4
TPSA:	78.87
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.485
Synthetic Accessibility Score:	4.818
Fsp3:	0.429
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:	-5.113
MDCK Permeability:	1.5090289707586635e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.117
Human Intestinal Absorption (HIA):	0.513
20% Bioavailability (F20%):	0.031
30% Bioavailability (F30%):	0.258

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.959
Plasma Protein Binding (PPB):	60.34770202636719%
Volume Distribution (VD):	0.816
Pgp-substrate:	45.943748474121094%

ADMET: Metabolism

CYP1A2-inhibitor:	0.031
CYP1A2-substrate:	0.559
CYP2C19-inhibitor:	0.084
CYP2C19-substrate:	0.842
CYP2C9-inhibitor:	0.129
CYP2C9-substrate:	0.531
CYP2D6-inhibitor:	0.492
CYP2D6-substrate:	0.463
CYP3A4-inhibitor:	0.197
CYP3A4-substrate:	0.656

ADMET: Excretion

Clearance (CL):	2.283
Half-life (T1/2):	0.563

ADMET: Toxicity

hERG Blockers:	0.43
Human Hepatotoxicity (H-HT):	0.312
Drug-inuced Liver Injury (DILI):	0.511
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.828
Maximum Recommended Daily Dose:	0.932
Skin Sensitization:	0.714
Carcinogencity:	0.944
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.966

Download Data

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

Natural Product: NPC153694

Natural Product ID:	NPC153694
*Common Name:**	18,19-Dehydrocorynoxinic Acid B
IUPAC Name:	(E)-2-[(3R,6'S,7'S,8'aS)-6'-ethenyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoic acid
Synonyms:
Standard InCHIKey:	ZGSZUQKKUBVUPV-HCFCNZAZSA-N
Standard InCHI:	InChI=1S/C21H24N2O4/c1-3-13-11-23-9-8-21(16-6-4-5-7-17(16)22-20(21)26)18(23)10-14(13)15(12-27-2)19(24)25/h3-7,12-14,18H,1,8-11H2,2H3,(H,22,26)(H,24,25)/b15-12+/t13-,14+,18+,21-/m1/s1
SMILES:	C=C[C@@H]1CN2CC[C@@]3(c4ccccc4N=C3O)[C@@H]2C[C@@H]1/C(=COC)/C(=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL481352
PubChem CID:	24970641
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
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10869194]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	leaves	n.a.	n.a.	PMID[18588343]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19331340]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21070010]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21070010]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27700077]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28225280]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31789520]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31804070]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13989	Uncaria macrophylla	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]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13989	Uncaria macrophylla	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]
NPO13989	Uncaria macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29352	Uncaria sinensis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14112	Uncaria rhynchophylla	Species	Rubiaceae	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	1
Others	4

Activity Type	# Activity
Others	5

Target ID	Target Type	Target Name	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	Inhibition	=	24.9	%	PMID[479488]
NPT2	Others	Unspecified	Inhibition	=	81.9	%	PMID[479488]
NPT2	Others	Unspecified	Inhibition	=	84.2	%	PMID[479488]
NPT2	Others	Unspecified	Inhibition	=	88.9	%	PMID[479488]
NPT2	Others	Unspecified	IC50	>	100000.0	nM	PMID[479488]

☑ 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 NPC153694 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	179
0.1-0.2	843
0.2-0.3	2944
0.3-0.4	11640
0.4-0.5	19149
0.5-0.6	6295
0.6-0.7	1467
0.7-0.8	154
0.8-0.85	6
0.85-0.9	2
0.9-0.95	7
0.95-1	11

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC211525
0.9796	High Similarity	NPC310403
0.9796	High Similarity	NPC97380
0.9796	High Similarity	NPC243673
0.9796	High Similarity	NPC148468
0.9796	High Similarity	NPC63210
0.9796	High Similarity	NPC263709
0.9592	High Similarity	NPC161827
0.9536	High Similarity	NPC470069
0.9536	High Similarity	NPC52059
0.9231	High Similarity	NPC21752
0.9231	High Similarity	NPC276993
0.9231	High Similarity	NPC298851
0.9231	High Similarity	NPC210415
0.9231	High Similarity	NPC181138
0.9231	High Similarity	NPC293255
0.8903	High Similarity	NPC472121
0.8272	Intermediate Similarity	NPC278887
0.8129	Intermediate Similarity	NPC472100
0.8	Intermediate Similarity	NPC472103
0.8	Intermediate Similarity	NPC475962
0.7943	Intermediate Similarity	NPC28510
0.7914	Intermediate Similarity	NPC474058
0.7888	Intermediate Similarity	NPC473297
0.7784	Intermediate Similarity	NPC469462
0.7765	Intermediate Similarity	NPC476441
0.7759	Intermediate Similarity	NPC469460
0.7744	Intermediate Similarity	NPC36495
0.7742	Intermediate Similarity	NPC243162
0.7725	Intermediate Similarity	NPC472115
0.7725	Intermediate Similarity	NPC472114
0.7716	Intermediate Similarity	NPC478076
0.7706	Intermediate Similarity	NPC13367
0.7697	Intermediate Similarity	NPC204970
0.7654	Intermediate Similarity	NPC203972
0.7647	Intermediate Similarity	NPC476425
0.7635	Intermediate Similarity	NPC317758
0.7614	Intermediate Similarity	NPC282092
0.759	Intermediate Similarity	NPC225319
0.759	Intermediate Similarity	NPC143457
0.7584	Intermediate Similarity	NPC174629
0.753	Intermediate Similarity	NPC193410
0.7529	Intermediate Similarity	NPC39822
0.7515	Intermediate Similarity	NPC214960
0.7515	Intermediate Similarity	NPC279527
0.7486	Intermediate Similarity	NPC476428
0.7485	Intermediate Similarity	NPC248117
0.7471	Intermediate Similarity	NPC99043
0.7471	Intermediate Similarity	NPC218594
0.747	Intermediate Similarity	NPC61013
0.7458	Intermediate Similarity	NPC472209
0.744	Intermediate Similarity	NPC282339
0.744	Intermediate Similarity	NPC472117
0.744	Intermediate Similarity	NPC99632
0.7425	Intermediate Similarity	NPC469461
0.7419	Intermediate Similarity	NPC474077
0.7416	Intermediate Similarity	NPC291759
0.741	Intermediate Similarity	NPC29285
0.7401	Intermediate Similarity	NPC245741
0.7365	Intermediate Similarity	NPC113946
0.736	Intermediate Similarity	NPC133591
0.7356	Intermediate Similarity	NPC203202
0.7356	Intermediate Similarity	NPC264482
0.7337	Intermediate Similarity	NPC472101
0.7337	Intermediate Similarity	NPC472120
0.7318	Intermediate Similarity	NPC38823
0.7318	Intermediate Similarity	NPC207033
0.7314	Intermediate Similarity	NPC476326
0.7303	Intermediate Similarity	NPC97584
0.7294	Intermediate Similarity	NPC313757
0.7278	Intermediate Similarity	NPC309531
0.7278	Intermediate Similarity	NPC472102
0.7273	Intermediate Similarity	NPC6974
0.7267	Intermediate Similarity	NPC224970
0.7267	Intermediate Similarity	NPC167724
0.7267	Intermediate Similarity	NPC223595
0.7262	Intermediate Similarity	NPC123241
0.7251	Intermediate Similarity	NPC472106
0.7243	Intermediate Similarity	NPC302548
0.7243	Intermediate Similarity	NPC475559
0.7235	Intermediate Similarity	NPC476231
0.7216	Intermediate Similarity	NPC186669
0.7207	Intermediate Similarity	NPC472119
0.7202	Intermediate Similarity	NPC477156
0.7202	Intermediate Similarity	NPC477157
0.7198	Intermediate Similarity	NPC5630
0.7182	Intermediate Similarity	NPC472323
0.7158	Intermediate Similarity	NPC203628
0.7151	Intermediate Similarity	NPC159963
0.7143	Intermediate Similarity	NPC102338
0.7143	Intermediate Similarity	NPC478079
0.7143	Intermediate Similarity	NPC63199
0.7143	Intermediate Similarity	NPC111602
0.7143	Intermediate Similarity	NPC196251
0.7135	Intermediate Similarity	NPC176983
0.7135	Intermediate Similarity	NPC286871
0.7135	Intermediate Similarity	NPC293458
0.7118	Intermediate Similarity	NPC471122
0.7111	Intermediate Similarity	NPC258480
0.7088	Intermediate Similarity	NPC21425
0.7088	Intermediate Similarity	NPC14994
0.7076	Intermediate Similarity	NPC201424
0.7073	Intermediate Similarity	NPC116519
0.7072	Intermediate Similarity	NPC52262
0.7065	Intermediate Similarity	NPC25401
0.7059	Intermediate Similarity	NPC90967
0.7053	Intermediate Similarity	NPC1464
0.7039	Intermediate Similarity	NPC15840
0.7029	Intermediate Similarity	NPC472118
0.7021	Intermediate Similarity	NPC265642
0.7021	Intermediate Similarity	NPC138615
0.7021	Intermediate Similarity	NPC218733
0.7021	Intermediate Similarity	NPC52557
0.7021	Intermediate Similarity	NPC132874
0.7011	Intermediate Similarity	NPC105055
0.7011	Intermediate Similarity	NPC473298
0.7011	Intermediate Similarity	NPC22689
0.7006	Intermediate Similarity	NPC329338
0.7006	Intermediate Similarity	NPC469726
0.7005	Intermediate Similarity	NPC303214
0.7	Intermediate Similarity	NPC232600
0.7	Intermediate Similarity	NPC113626
0.6995	Remote Similarity	NPC181928
0.6995	Remote Similarity	NPC473815
0.6994	Remote Similarity	NPC189116
0.6983	Remote Similarity	NPC321211
0.6979	Remote Similarity	NPC14339
0.6978	Remote Similarity	NPC322621
0.6977	Remote Similarity	NPC315368
0.6975	Remote Similarity	NPC315051
0.6961	Remote Similarity	NPC159125
0.6961	Remote Similarity	NPC477159
0.6957	Remote Similarity	NPC175474
0.6954	Remote Similarity	NPC471124
0.6952	Remote Similarity	NPC221687
0.6949	Remote Similarity	NPC285622
0.6949	Remote Similarity	NPC139085
0.6949	Remote Similarity	NPC251212
0.6949	Remote Similarity	NPC214626
0.6943	Remote Similarity	NPC246140
0.6943	Remote Similarity	NPC195787
0.694	Remote Similarity	NPC66210
0.6935	Remote Similarity	NPC55493
0.6932	Remote Similarity	NPC469915
0.6931	Remote Similarity	NPC100863
0.6928	Remote Similarity	NPC291027
0.6928	Remote Similarity	NPC478039
0.6928	Remote Similarity	NPC84281
0.6928	Remote Similarity	NPC317474
0.6928	Remote Similarity	NPC213126
0.6928	Remote Similarity	NPC169485
0.6928	Remote Similarity	NPC264589
0.6927	Remote Similarity	NPC234987
0.6919	Remote Similarity	NPC314333
0.6919	Remote Similarity	NPC472112
0.6919	Remote Similarity	NPC329858
0.6915	Remote Similarity	NPC245916
0.6911	Remote Similarity	NPC469732
0.6907	Remote Similarity	NPC53344
0.6903	Remote Similarity	NPC205946
0.6899	Remote Similarity	NPC314098
0.6899	Remote Similarity	NPC316746
0.6895	Remote Similarity	NPC241024
0.6893	Remote Similarity	NPC355
0.6891	Remote Similarity	NPC87714
0.6887	Remote Similarity	NPC264580
0.6885	Remote Similarity	NPC473007
0.6882	Remote Similarity	NPC22476
0.6879	Remote Similarity	NPC477158
0.6875	Remote Similarity	NPC162730
0.6872	Remote Similarity	NPC129624
0.6865	Remote Similarity	NPC217294
0.6865	Remote Similarity	NPC284706
0.6864	Remote Similarity	NPC154602
0.6862	Remote Similarity	NPC34717
0.6862	Remote Similarity	NPC289299
0.6862	Remote Similarity	NPC57994
0.6859	Remote Similarity	NPC254240
0.6859	Remote Similarity	NPC475489
0.6859	Remote Similarity	NPC294909
0.6859	Remote Similarity	NPC128265
0.6859	Remote Similarity	NPC312870
0.6859	Remote Similarity	NPC199851
0.6854	Remote Similarity	NPC96901
0.6852	Remote Similarity	NPC281104
0.6846	Remote Similarity	NPC470550
0.6845	Remote Similarity	NPC300596
0.6845	Remote Similarity	NPC237649
0.6839	Remote Similarity	NPC85651
0.6837	Remote Similarity	NPC469743
0.6828	Remote Similarity	NPC473008
0.6828	Remote Similarity	NPC474059
0.6825	Remote Similarity	NPC473375
0.6825	Remote Similarity	NPC97100
0.681	Remote Similarity	NPC469560
0.6802	Remote Similarity	NPC269449
0.68	Remote Similarity	NPC469928
0.6795	Remote Similarity	NPC325013
0.679	Remote Similarity	NPC208725
0.6788	Remote Similarity	NPC474116

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 NPC153694 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	404
0.2-0.3	655
0.3-0.4	1085
0.4-0.5	3038
0.5-0.6	3158
0.6-0.7	664
0.7-0.8	17
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
0.7308	Intermediate Similarity	NPD5184	Approved
0.7308	Intermediate Similarity	NPD5182	Approved
0.7308	Intermediate Similarity	NPD5185	Approved
0.7219	Intermediate Similarity	NPD7599	Phase 2
0.7178	Intermediate Similarity	NPD5595	Clinical (unspecified phase)
0.7176	Intermediate Similarity	NPD7600	Phase 2
0.7168	Intermediate Similarity	NPD2844	Phase 3
0.7114	Intermediate Similarity	NPD2994	Approved
0.7083	Intermediate Similarity	NPD4121	Phase 3
0.7083	Intermediate Similarity	NPD4120	Approved
0.7067	Intermediate Similarity	NPD2210	Approved
0.7067	Intermediate Similarity	NPD2212	Approved
0.7047	Intermediate Similarity	NPD2116	Approved
0.7047	Intermediate Similarity	NPD2117	Pre-registration
0.7047	Intermediate Similarity	NPD2115	Approved
0.7041	Intermediate Similarity	NPD5743	Approved
0.7041	Intermediate Similarity	NPD5742	Approved
0.7041	Intermediate Similarity	NPD5741	Approved
0.7019	Intermediate Similarity	NPD3170	Approved
0.6995	Remote Similarity	NPD8103	Clinical (unspecified phase)
0.6974	Remote Similarity	NPD2946	Phase 2
0.6959	Remote Similarity	NPD5715	Clinical (unspecified phase)
0.6954	Remote Similarity	NPD3031	Approved
0.6954	Remote Similarity	NPD3030	Approved
0.6954	Remote Similarity	NPD3032	Approved
0.6951	Remote Similarity	NPD2820	Phase 3
0.6946	Remote Similarity	NPD4682	Phase 2
0.6941	Remote Similarity	NPD7463	Clinical (unspecified phase)
0.6928	Remote Similarity	NPD2608	Approved
0.6928	Remote Similarity	NPD4218	Approved
0.6928	Remote Similarity	NPD4217	Approved
0.6928	Remote Similarity	NPD2610	Approved
0.6928	Remote Similarity	NPD4215	Approved
0.6928	Remote Similarity	NPD2612	Approved
0.6928	Remote Similarity	NPD2611	Approved
0.6928	Remote Similarity	NPD3132	Approved
0.6928	Remote Similarity	NPD6416	Phase 2
0.6928	Remote Similarity	NPD3131	Approved
0.6928	Remote Similarity	NPD2609	Approved
0.6928	Remote Similarity	NPD4216	Approved
0.6919	Remote Similarity	NPD4499	Approved
0.689	Remote Similarity	NPD2365	Approved
0.6868	Remote Similarity	NPD7252	Clinical (unspecified phase)
0.6862	Remote Similarity	NPD4602	Approved
0.6859	Remote Similarity	NPD4501	Approved
0.6859	Remote Similarity	NPD4500	Approved
0.6857	Remote Similarity	NPD7591	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD2569	Approved
0.6852	Remote Similarity	NPD2567	Approved
0.6852	Remote Similarity	NPD2670	Approved
0.6845	Remote Similarity	NPD7570	Approved
0.6845	Remote Similarity	NPD7569	Approved
0.6836	Remote Similarity	NPD7795	Phase 2
0.6835	Remote Similarity	NPD6359	Clinical (unspecified phase)
0.6806	Remote Similarity	NPD7000	Clinical (unspecified phase)
0.6806	Remote Similarity	NPD6999	Discontinued
0.6791	Remote Similarity	NPD5076	Approved
0.6791	Remote Similarity	NPD5077	Approved
0.6765	Remote Similarity	NPD3329	Clinical (unspecified phase)
0.6763	Remote Similarity	NPD3589	Clinical (unspecified phase)
0.674	Remote Similarity	NPD8006	Clinical (unspecified phase)
0.673	Remote Similarity	NPD2613	Approved
0.6719	Remote Similarity	NPD6874	Approved
0.6711	Remote Similarity	NPD2607	Approved
0.6711	Remote Similarity	NPD181	Approved
0.6707	Remote Similarity	NPD1110	Approved
0.6707	Remote Similarity	NPD6655	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD1109	Approved
0.6701	Remote Similarity	NPD5721	Clinical (unspecified phase)
0.6689	Remote Similarity	NPD2622	Approved
0.6688	Remote Similarity	NPD5578	Approved
0.6688	Remote Similarity	NPD5577	Clinical (unspecified phase)
0.6688	Remote Similarity	NPD6325	Discontinued
0.6688	Remote Similarity	NPD1036	Approved
0.6686	Remote Similarity	NPD5811	Approved
0.6685	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6684	Remote Similarity	NPD6732	Clinical (unspecified phase)
0.6684	Remote Similarity	NPD4600	Approved
0.6684	Remote Similarity	NPD4601	Approved
0.6684	Remote Similarity	NPD7001	Phase 3
0.6667	Remote Similarity	NPD3147	Approved
0.6667	Remote Similarity	NPD5430	Discontinued
0.6667	Remote Similarity	NPD6878	Phase 2
0.6667	Remote Similarity	NPD2658	Approved
0.6667	Remote Similarity	NPD3149	Approved
0.6667	Remote Similarity	NPD2659	Approved
0.6667	Remote Similarity	NPD4397	Phase 1
0.6667	Remote Similarity	NPD3812	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6879	Phase 2
0.6667	Remote Similarity	NPD6017	Discontinued
0.6667	Remote Similarity	NPD3148	Approved
0.6667	Remote Similarity	NPD8416	Discontinued
0.6667	Remote Similarity	NPD3150	Approved
0.6667	Remote Similarity	NPD2584	Suspended
0.6648	Remote Similarity	NPD3376	Clinical (unspecified phase)
0.6646	Remote Similarity	NPD2628	Approved
0.6646	Remote Similarity	NPD2626	Approved
0.6646	Remote Similarity	NPD2625	Approved
0.6646	Remote Similarity	NPD2159	Approved
0.6646	Remote Similarity	NPD2160	Approved
0.6646	Remote Similarity	NPD2627	Approved
0.663	Remote Similarity	NPD3423	Phase 2
0.663	Remote Similarity	NPD3422	Phase 3
0.663	Remote Similarity	NPD5466	Approved
0.6629	Remote Similarity	NPD4335	Clinical (unspecified phase)
0.6627	Remote Similarity	NPD3625	Discontinued
0.6627	Remote Similarity	NPD4041	Approved
0.6626	Remote Similarity	NPD8643	Discontinued
0.6623	Remote Similarity	NPD5631	Phase 3
0.6622	Remote Similarity	NPD1756	Approved
0.6622	Remote Similarity	NPD1752	Approved
0.6609	Remote Similarity	NPD1663	Discontinued
0.6607	Remote Similarity	NPD2435	Approved
0.6607	Remote Similarity	NPD6506	Clinical (unspecified phase)
0.6605	Remote Similarity	NPD2566	Approved
0.6605	Remote Similarity	NPD2570	Approved
0.6605	Remote Similarity	NPD2571	Approved
0.6605	Remote Similarity	NPD3089	Approved
0.6605	Remote Similarity	NPD4745	Approved
0.6605	Remote Similarity	NPD3090	Approved
0.6605	Remote Similarity	NPD3088	Approved
0.6605	Remote Similarity	NPD2574	Discontinued
0.6605	Remote Similarity	NPD3615	Approved
0.6605	Remote Similarity	NPD4746	Phase 3
0.6605	Remote Similarity	NPD3614	Approved
0.6605	Remote Similarity	NPD2573	Approved
0.6605	Remote Similarity	NPD3616	Approved
0.6605	Remote Similarity	NPD3087	Approved
0.6605	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.66	Remote Similarity	NPD1762	Approved
0.66	Remote Similarity	NPD1764	Approved
0.6596	Remote Similarity	NPD6608	Clinical (unspecified phase)
0.6591	Remote Similarity	NPD2506	Approved
0.6588	Remote Similarity	NPD1802	Approved
0.6588	Remote Similarity	NPD1801	Approved
0.6585	Remote Similarity	NPD6073	Approved
0.658	Remote Similarity	NPD4987	Clinical (unspecified phase)
0.658	Remote Similarity	NPD7777	Approved
0.658	Remote Similarity	NPD7778	Approved
0.658	Remote Similarity	NPD53	Approved
0.6579	Remote Similarity	NPD6665	Discontinued
0.6571	Remote Similarity	NPD7735	Clinical (unspecified phase)
0.657	Remote Similarity	NPD5982	Phase 2
0.6566	Remote Similarity	NPD989	Approved
0.6566	Remote Similarity	NPD4707	Clinical (unspecified phase)
0.6564	Remote Similarity	NPD6310	Approved
0.6564	Remote Similarity	NPD6309	Approved
0.6564	Remote Similarity	NPD6311	Approved
0.6561	Remote Similarity	NPD3623	Clinical (unspecified phase)
0.6561	Remote Similarity	NPD3622	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD5257	Clinical (unspecified phase)
0.655	Remote Similarity	NPD5941	Approved
0.655	Remote Similarity	NPD7528	Approved
0.655	Remote Similarity	NPD5942	Approved
0.655	Remote Similarity	NPD979	Approved
0.655	Remote Similarity	NPD5881	Clinical (unspecified phase)
0.655	Remote Similarity	NPD4432	Discontinued
0.6546	Remote Similarity	NPD6661	Clinical (unspecified phase)
0.6543	Remote Similarity	NPD4621	Approved
0.6543	Remote Similarity	NPD4619	Approved
0.6543	Remote Similarity	NPD4948	Discontinued
0.6541	Remote Similarity	NPD7149	Clinical (unspecified phase)
0.6534	Remote Similarity	NPD7114	Clinical (unspecified phase)
0.6533	Remote Similarity	NPD7665	Phase 2
0.6533	Remote Similarity	NPD7666	Phase 3
0.6532	Remote Similarity	NPD2948	Discontinued
0.6528	Remote Similarity	NPD7238	Clinical (unspecified phase)
0.6526	Remote Similarity	NPD5042	Phase 1
0.6524	Remote Similarity	NPD4686	Approved
0.6524	Remote Similarity	NPD4684	Phase 3
0.6524	Remote Similarity	NPD4685	Phase 3
0.6522	Remote Similarity	NPD5263	Approved
0.6519	Remote Similarity	NPD1165	Clinical (unspecified phase)
0.6517	Remote Similarity	NPD5088	Discontinued
0.6516	Remote Similarity	NPD5981	Approved
0.6515	Remote Similarity	NPD7174	Clinical (unspecified phase)
0.6514	Remote Similarity	NPD6913	Approved
0.6514	Remote Similarity	NPD7105	Phase 1
0.6503	Remote Similarity	NPD7715	Approved
0.6503	Remote Similarity	NPD7714	Approved
0.65	Remote Similarity	NPD3983	Phase 3
0.65	Remote Similarity	NPD3984	Clinical (unspecified phase)
0.6497	Remote Similarity	NPD7205	Discontinued
0.6492	Remote Similarity	NPD8146	Phase 2
0.6488	Remote Similarity	NPD6414	Clinical (unspecified phase)
0.6486	Remote Similarity	NPD6833	Clinical (unspecified phase)
0.6486	Remote Similarity	NPD5445	Approved
0.6485	Remote Similarity	NPD6657	Clinical (unspecified phase)
0.6485	Remote Similarity	NPD8173	Phase 2
0.6485	Remote Similarity	NPD5725	Approved
0.6485	Remote Similarity	NPD8172	Phase 2
0.6484	Remote Similarity	NPD750	Phase 2
0.6481	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.6481	Remote Similarity	NPD4738	Phase 2
0.648	Remote Similarity	NPD4796	Discontinued
0.6477	Remote Similarity	NPD7818	Clinical (unspecified phase)
0.6477	Remote Similarity	NPD7011	Discontinued
0.6471	Remote Similarity	NPD4412	Phase 2
0.6471	Remote Similarity	NPD2887	Clinical (unspecified phase)
0.6468	Remote Similarity	NPD4900	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