NPASS Compound

Structure

NPC129486 OpenBabel07101718242D 59 61 0 0 1 0 0 0 0 0999 V2000 6.4255 5.6082 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6092 -7.1965 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0230 -6.5007 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4286 5.7184 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0375 -2.0318 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8786 4.7710 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0389 4.1978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6178 -0.0268 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0631 4.4165 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3246 0.9293 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2094 0.5798 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7094 -0.2862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5448 0.4595 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7094 -0.2862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2094 -1.1523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0689 -0.4200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3374 3.2434 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7992 -0.6011 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4186 -5.4749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7094 1.4458 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4208 -1.5816 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0169 -6.3907 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8801 4.8261 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6358 -2.9476 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.2094 0.5798 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7094 1.4458 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2094 -1.1523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6142 3.6808 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4514 -1.3361 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3247 0.9458 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3331 -1.0973 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8264 -4.6692 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3331 3.9889 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4514 4.2277 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6419 -3.0576 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3247 1.9458 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0689 3.3117 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4208 4.4732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6142 -0.7891 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6117 2.0703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5875 1.8516 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.9344 1.3346 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3132 3.0247 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4174 -1.4990 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.2281 -3.7534 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.5448 2.4322 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.8916 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0497 -2.2519 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4174 4.3906 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.7094 -2.0183 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8801 -1.9345 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8325 -4.7792 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0497 5.1435 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2402 -3.9734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3111 2.1104 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8580 3.9259 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3382 5.4698 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0631 -1.5249 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 22 1 0 0 0 0 3 22 1 0 0 0 0 6 23 1 0 0 0 0 7 9 1 0 0 0 0 7 17 1 0 0 0 0 8 10 1 0 0 0 0 8 18 1 0 0 0 0 11 14 1 0 0 0 0 11 25 2 0 0 0 0 12 15 2 0 0 0 0 12 25 1 0 0 0 0 13 16 2 0 0 0 0 13 26 1 0 0 0 0 14 27 2 0 0 0 0 15 27 1 0 0 0 0 16 31 1 0 0 0 0 17 43 1 0 0 0 0 18 50 1 0 0 0 0 19 22 1 0 0 0 0 19 32 1 0 0 0 0 20 25 1 0 0 0 0 21 29 1 0 0 0 0 21 44 1 0 0 0 0 23 4 1 1 0 0 0 24 5 1 6 0 0 0 24 35 1 0 0 0 0 24 45 1 0 0 0 0 26 20 1 1 0 0 0 26 46 1 0 0 0 0 27 51 1 0 0 0 0 28 9 1 1 0 0 0 28 34 1 0 0 0 0 28 47 1 0 0 0 0 29 39 1 0 0 0 0 29 48 1 6 0 0 0 30 10 1 1 0 0 0 30 36 1 0 0 0 0 30 50 1 0 0 0 0 31 44 2 3 0 0 0 31 52 1 0 0 0 0 32 45 2 3 0 0 0 32 53 1 0 0 0 0 33 23 1 6 0 0 0 33 37 1 0 0 0 0 33 49 1 0 0 0 0 34 38 1 0 0 0 0 34 54 2 0 0 0 0 35 48 2 3 0 0 0 35 55 1 0 0 0 0 36 47 2 3 0 0 0 36 56 1 0 0 0 0 37 46 2 3 0 0 0 37 57 1 0 0 0 0 38 49 1 0 0 0 0 38 58 2 0 0 0 0 39 50 1 0 0 0 0 39 59 2 0 0 0 0 40 41 2 0 0 0 0 40 42 1 0 0 0 0 40 43 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	824.45
Volume:	829.532
LogP:	-0.101
LogD:	0.388
LogS:	-3.475
# Rotatable Bonds:	16
TPSA:	297.6
# H-Bond Aceptor:	19
# H-Bond Donor:	11
# Rings:	3
# Heavy Atoms:	19

MedChem Properties

QED Drug-Likeness Score:	0.054
Synthetic Accessibility Score:	5.844
Fsp3:	0.575
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.866
MDCK Permeability:	8.305191840918269e-06
Pgp-inhibitor:	0.082
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.976
20% Bioavailability (F20%):	0.994
30% Bioavailability (F30%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.062
Plasma Protein Binding (PPB):	25.480979919433594%
Volume Distribution (VD):	0.387
Pgp-substrate:	63.52848815917969%

ADMET: Metabolism

CYP1A2-inhibitor:	0.0
CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.04
CYP2C19-substrate:	0.036
CYP2C9-inhibitor:	0.105
CYP2C9-substrate:	0.042
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.104
CYP3A4-inhibitor:	0.039
CYP3A4-substrate:	0.012

ADMET: Excretion

Clearance (CL):	2.872
Half-life (T1/2):	0.602

ADMET: Toxicity

hERG Blockers:	0.089
Human Hepatotoxicity (H-HT):	0.798
Drug-inuced Liver Injury (DILI):	0.624
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.177
Maximum Recommended Daily Dose:	0.966
Skin Sensitization:	0.205
Carcinogencity:	0.289
Eye Corrosion:	0.003
Eye Irritation:	0.004
Respiratory Toxicity:	0.939

Download Data

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

Natural Product: NPC129486

Natural Product ID:	NPC129486
*Common Name:**	Cyclotheonamide E3
IUPAC Name:	N-[(2S)-1-[[(3S,7E,9S,12R,16S,19S)-12-[(2S)-butan-2-yl]-16-[3-(diaminomethylideneamino)propyl]-9-[(4-hydroxyphenyl)methyl]-2,6,11,14,15,18-hexaoxo-1,5,10,13,17-pentazabicyclo[17.3.0]docos-7-en-3-yl]amino]-1-oxopropan-2-yl]-3-methylbutanamide
Synonyms:	Cyclotheonamide E3
Standard InCHIKey:	ARWQONCLAGEDMW-VGOQXBOYSA-N
Standard InCHI:	InChI=1S/C40H60N10O9/c1-6-23(4)33-37(57)46-26(20-25-11-14-27(51)15-12-25)13-16-31(52)44-21-29(48-35(55)24(5)45-32(53)19-22(2)3)39(59)50-18-8-10-30(50)36(56)47-28(34(54)38(58)49-33)9-7-17-43-40(41)42/h11-16,22-24,26,28-30,33,51H,6-10,17-21H2,1-5H3,(H,44,52)(H,45,53)(H,46,57)(H,47,56)(H,48,55)(H,49,58)(H4,41,42,43)/b16-13+/t23-,24-,26+,28-,29-,30-,33+/m0/s1
SMILES:	CC[C@H](C)[C@@H]1C(=N[C@H](/C=C/C(=NC[C@@H](C(=O)N2CCC[C@H]2C(=N[C@@H](CCCNC(=N)N)C(=O)C(=O)N1)O)N=C([C@H](C)N=C(CC(C)C)O)O)O)Cc1ccc(cc1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL448342
PubChem CID:	12041284
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

*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
NPO33174	theonella	Genus	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9599274]

☑ 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

Activity Type	# Activity
Individual Protein	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT670	Individual Protein	Thrombin	Homo sapiens	IC50	=	9.5	nM	PMID[451362]
NPT2	Others	Unspecified		IC50	=	52.0	nM	PMID[451362]

☑ 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 NPC129486 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	238
0.1-0.2	1630
0.2-0.3	10335
0.3-0.4	8520
0.4-0.5	17531
0.5-0.6	3513
0.6-0.7	637
0.7-0.8	229
0.8-0.85	46
0.85-0.9	12
0.9-0.95	2
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9806	High Similarity	NPC475532
0.9744	High Similarity	NPC165285
0.9494	High Similarity	NPC17698
0.8944	High Similarity	NPC198254
0.8944	High Similarity	NPC274198
0.8827	High Similarity	NPC276506
0.8727	High Similarity	NPC196243
0.865	High Similarity	NPC280022
0.8608	High Similarity	NPC473580
0.8509	High Similarity	NPC469243
0.8481	Intermediate Similarity	NPC261934
0.8481	Intermediate Similarity	NPC5194
0.8481	Intermediate Similarity	NPC56685
0.8462	Intermediate Similarity	NPC153554
0.8412	Intermediate Similarity	NPC473404
0.8402	Intermediate Similarity	NPC119652
0.8402	Intermediate Similarity	NPC97526
0.8397	Intermediate Similarity	NPC311658
0.8397	Intermediate Similarity	NPC16188
0.8395	Intermediate Similarity	NPC475544
0.8365	Intermediate Similarity	NPC262166
0.8365	Intermediate Similarity	NPC202198
0.8354	Intermediate Similarity	NPC223207
0.8303	Intermediate Similarity	NPC290755
0.8303	Intermediate Similarity	NPC304074
0.8303	Intermediate Similarity	NPC471771
0.8302	Intermediate Similarity	NPC233702
0.8286	Intermediate Similarity	NPC240130
0.8286	Intermediate Similarity	NPC61332
0.8272	Intermediate Similarity	NPC323336
0.8272	Intermediate Similarity	NPC326349
0.8253	Intermediate Similarity	NPC328649
0.8232	Intermediate Similarity	NPC241794
0.8194	Intermediate Similarity	NPC476989
0.8193	Intermediate Similarity	NPC61004
0.8171	Intermediate Similarity	NPC94862
0.8148	Intermediate Similarity	NPC244509
0.814	Intermediate Similarity	NPC170302
0.814	Intermediate Similarity	NPC475409
0.814	Intermediate Similarity	NPC475564
0.8133	Intermediate Similarity	NPC63931
0.8129	Intermediate Similarity	NPC48202
0.8125	Intermediate Similarity	NPC102959
0.8095	Intermediate Similarity	NPC66490
0.8079	Intermediate Similarity	NPC60516
0.8047	Intermediate Similarity	NPC475123
0.8047	Intermediate Similarity	NPC475204
0.8045	Intermediate Similarity	NPC302715
0.8036	Intermediate Similarity	NPC141957
0.8023	Intermediate Similarity	NPC473546
0.8012	Intermediate Similarity	NPC473491
0.8	Intermediate Similarity	NPC477638
0.8	Intermediate Similarity	NPC244336
0.8	Intermediate Similarity	NPC477632
0.7978	Intermediate Similarity	NPC477636
0.7949	Intermediate Similarity	NPC242159
0.7949	Intermediate Similarity	NPC313694
0.7941	Intermediate Similarity	NPC46009
0.7929	Intermediate Similarity	NPC302597
0.7889	Intermediate Similarity	NPC477631
0.7871	Intermediate Similarity	NPC267237
0.7865	Intermediate Similarity	NPC96275
0.7857	Intermediate Similarity	NPC477639
0.7849	Intermediate Similarity	NPC137627
0.7818	Intermediate Similarity	NPC476268
0.7803	Intermediate Similarity	NPC26108
0.7778	Intermediate Similarity	NPC51047
0.7772	Intermediate Similarity	NPC477550
0.7772	Intermediate Similarity	NPC477552
0.776	Intermediate Similarity	NPC329295
0.7746	Intermediate Similarity	NPC306804
0.7701	Intermediate Similarity	NPC471165
0.7688	Intermediate Similarity	NPC469443
0.7688	Intermediate Similarity	NPC328494
0.7688	Intermediate Similarity	NPC477551
0.7683	Intermediate Similarity	NPC324081
0.7673	Intermediate Similarity	NPC214988
0.767	Intermediate Similarity	NPC269750
0.767	Intermediate Similarity	NPC194671
0.7633	Intermediate Similarity	NPC114806
0.7624	Intermediate Similarity	NPC246591
0.76	Intermediate Similarity	NPC279871
0.76	Intermediate Similarity	NPC136797
0.7586	Intermediate Similarity	NPC89831
0.7574	Intermediate Similarity	NPC24617
0.7557	Intermediate Similarity	NPC50016
0.7556	Intermediate Similarity	NPC299806
0.7543	Intermediate Similarity	NPC273755
0.7541	Intermediate Similarity	NPC470728
0.753	Intermediate Similarity	NPC300443
0.7529	Intermediate Similarity	NPC40234
0.7514	Intermediate Similarity	NPC107938
0.7514	Intermediate Similarity	NPC294516
0.7514	Intermediate Similarity	NPC80514
0.75	Intermediate Similarity	NPC472923
0.75	Intermediate Similarity	NPC476227
0.7486	Intermediate Similarity	NPC477637
0.7486	Intermediate Similarity	NPC230611
0.7472	Intermediate Similarity	NPC45037
0.7471	Intermediate Similarity	NPC319320
0.7471	Intermediate Similarity	NPC287757
0.7469	Intermediate Similarity	NPC168861
0.7448	Intermediate Similarity	NPC220060
0.7439	Intermediate Similarity	NPC81026
0.7423	Intermediate Similarity	NPC326241
0.7414	Intermediate Similarity	NPC209463
0.7412	Intermediate Similarity	NPC324850
0.7409	Intermediate Similarity	NPC478005
0.7409	Intermediate Similarity	NPC469444
0.7405	Intermediate Similarity	NPC326966
0.7401	Intermediate Similarity	NPC473402
0.7401	Intermediate Similarity	NPC155506
0.7401	Intermediate Similarity	NPC159767
0.7391	Intermediate Similarity	NPC132636
0.7378	Intermediate Similarity	NPC266741
0.7368	Intermediate Similarity	NPC1390
0.7368	Intermediate Similarity	NPC62104
0.7345	Intermediate Similarity	NPC248670
0.7341	Intermediate Similarity	NPC289776
0.7341	Intermediate Similarity	NPC133470
0.7341	Intermediate Similarity	NPC191863
0.7337	Intermediate Similarity	NPC39431
0.7329	Intermediate Similarity	NPC109580
0.7316	Intermediate Similarity	NPC473450
0.7308	Intermediate Similarity	NPC294951
0.7303	Intermediate Similarity	NPC283760
0.7303	Intermediate Similarity	NPC473354
0.7296	Intermediate Similarity	NPC469445
0.7296	Intermediate Similarity	NPC257390
0.7278	Intermediate Similarity	NPC475421
0.7273	Intermediate Similarity	NPC186617
0.7268	Intermediate Similarity	NPC219350
0.7268	Intermediate Similarity	NPC194699
0.7262	Intermediate Similarity	NPC475168
0.7262	Intermediate Similarity	NPC7817
0.7257	Intermediate Similarity	NPC254700
0.7255	Intermediate Similarity	NPC200964
0.7233	Intermediate Similarity	NPC130309
0.7233	Intermediate Similarity	NPC255447
0.7232	Intermediate Similarity	NPC471568
0.7232	Intermediate Similarity	NPC473693
0.7207	Intermediate Similarity	NPC158277
0.72	Intermediate Similarity	NPC22883
0.72	Intermediate Similarity	NPC210377
0.72	Intermediate Similarity	NPC5719
0.72	Intermediate Similarity	NPC217804
0.7189	Intermediate Similarity	NPC329731
0.7186	Intermediate Similarity	NPC119569
0.7178	Intermediate Similarity	NPC478007
0.717	Intermediate Similarity	NPC325651
0.7169	Intermediate Similarity	NPC316008
0.7169	Intermediate Similarity	NPC313867
0.716	Intermediate Similarity	NPC314835
0.7159	Intermediate Similarity	NPC15068
0.7158	Intermediate Similarity	NPC470903
0.7158	Intermediate Similarity	NPC470112
0.7158	Intermediate Similarity	NPC167763
0.7143	Intermediate Similarity	NPC184933
0.7143	Intermediate Similarity	NPC59827
0.7136	Intermediate Similarity	NPC323244
0.7135	Intermediate Similarity	NPC470902
0.7126	Intermediate Similarity	NPC473804
0.7126	Intermediate Similarity	NPC314358
0.7121	Intermediate Similarity	NPC277306
0.7121	Intermediate Similarity	NPC469442
0.712	Intermediate Similarity	NPC471050
0.712	Intermediate Similarity	NPC471049
0.712	Intermediate Similarity	NPC471048
0.7119	Intermediate Similarity	NPC63040
0.7115	Intermediate Similarity	NPC6975
0.7112	Intermediate Similarity	NPC163961
0.7112	Intermediate Similarity	NPC473305
0.7108	Intermediate Similarity	NPC314388
0.7108	Intermediate Similarity	NPC315283
0.7108	Intermediate Similarity	NPC478008
0.7107	Intermediate Similarity	NPC473322
0.7104	Intermediate Similarity	NPC476321
0.7101	Intermediate Similarity	NPC2501
0.7099	Intermediate Similarity	NPC141050
0.7097	Intermediate Similarity	NPC71684
0.7097	Intermediate Similarity	NPC4910
0.7093	Intermediate Similarity	NPC469903
0.709	Intermediate Similarity	NPC328763
0.7081	Intermediate Similarity	NPC138083
0.7081	Intermediate Similarity	NPC235194
0.7081	Intermediate Similarity	NPC328924
0.7079	Intermediate Similarity	NPC315388
0.7077	Intermediate Similarity	NPC81845
0.7074	Intermediate Similarity	NPC248822
0.7069	Intermediate Similarity	NPC469898
0.7066	Intermediate Similarity	NPC315266
0.7065	Intermediate Similarity	NPC471526
0.7063	Intermediate Similarity	NPC300315
0.7063	Intermediate Similarity	NPC478147
0.7051	Intermediate Similarity	NPC27581
0.705	Intermediate Similarity	NPC25539
0.7049	Intermediate Similarity	NPC472999
0.7049	Intermediate Similarity	NPC32064
0.7048	Intermediate Similarity	NPC91953
0.7039	Intermediate Similarity	NPC317254

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 NPC129486 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	149
0.1-0.2	417
0.2-0.3	794
0.3-0.4	1528
0.4-0.5	3904
0.5-0.6	2039
0.6-0.7	285
0.7-0.8	30
0.8-0.85	3
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9236	High Similarity	NPD8303	Discontinued
0.8365	Intermediate Similarity	NPD7523	Phase 3
0.8272	Intermediate Similarity	NPD7118	Clinical (unspecified phase)
0.8079	Intermediate Similarity	NPD7617	Discontinued
0.8	Intermediate Similarity	NPD7495	Discontinued
0.8	Intermediate Similarity	NPD8019	Approved
0.7911	Intermediate Similarity	NPD8076	Discontinued
0.7907	Intermediate Similarity	NPD5200	Clinical (unspecified phase)
0.7866	Intermediate Similarity	NPD6670	Clinical (unspecified phase)
0.7771	Intermediate Similarity	NPD4782	Clinical (unspecified phase)
0.7756	Intermediate Similarity	NPD4791	Clinical (unspecified phase)
0.7744	Intermediate Similarity	NPD6078	Clinical (unspecified phase)
0.7669	Intermediate Similarity	NPD8290	Clinical (unspecified phase)
0.763	Intermediate Similarity	NPD4652	Approved
0.761	Intermediate Similarity	NPD6901	Phase 3
0.7602	Intermediate Similarity	NPD2098	Approved
0.7546	Intermediate Similarity	NPD7066	Clinical (unspecified phase)
0.7485	Intermediate Similarity	NPD2097	Approved
0.7469	Intermediate Similarity	NPD6809	Clinical (unspecified phase)
0.7425	Intermediate Similarity	NPD7303	Discontinued
0.7423	Intermediate Similarity	NPD5341	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD7450	Phase 2
0.7405	Intermediate Similarity	NPD1330	Phase 2
0.7405	Intermediate Similarity	NPD3632	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD1329	Clinical (unspecified phase)
0.7375	Intermediate Similarity	NPD4757	Clinical (unspecified phase)
0.7372	Intermediate Similarity	NPD5339	Clinical (unspecified phase)
0.7365	Intermediate Similarity	NPD5348	Clinical (unspecified phase)
0.7346	Intermediate Similarity	NPD7728	Clinical (unspecified phase)
0.7233	Intermediate Similarity	NPD3136	Phase 2
0.722	Intermediate Similarity	NPD8292	Phase 2
0.7175	Intermediate Similarity	NPD7484	Phase 3
0.7175	Intermediate Similarity	NPD7485	Phase 3
0.717	Intermediate Similarity	NPD7979	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD7978	Discontinued
0.7108	Intermediate Similarity	NPD6681	Discovery
0.7101	Intermediate Similarity	NPD6682	Clinical (unspecified phase)
0.7095	Intermediate Similarity	NPD5137	Approved
0.7079	Intermediate Similarity	NPD2888	Approved
0.7079	Intermediate Similarity	NPD2890	Approved
0.7079	Intermediate Similarity	NPD2017	Approved
0.7079	Intermediate Similarity	NPD2889	Approved
0.7076	Intermediate Similarity	NPD7131	Phase 3
0.7037	Intermediate Similarity	NPD5729	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD3072	Approved
0.7006	Intermediate Similarity	NPD3073	Approved
0.7006	Intermediate Similarity	NPD3071	Approved
0.6978	Remote Similarity	NPD8022	Clinical (unspecified phase)
0.6943	Remote Similarity	NPD4761	Approved
0.6943	Remote Similarity	NPD4762	Approved
0.6928	Remote Similarity	NPD6867	Clinical (unspecified phase)
0.6928	Remote Similarity	NPD6866	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD7613	Discontinued
0.6914	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.6909	Remote Similarity	NPD8173	Phase 2
0.6909	Remote Similarity	NPD8172	Phase 2
0.6901	Remote Similarity	NPD6631	Clinical (unspecified phase)
0.6898	Remote Similarity	NPD5946	Clinical (unspecified phase)
0.6894	Remote Similarity	NPD3040	Approved
0.6881	Remote Similarity	NPD6188	Approved
0.6881	Remote Similarity	NPD6189	Approved
0.6864	Remote Similarity	NPD6860	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD5263	Approved
0.6852	Remote Similarity	NPD4676	Approved
0.6848	Remote Similarity	NPD7113	Clinical (unspecified phase)
0.6837	Remote Similarity	NPD6255	Approved
0.6837	Remote Similarity	NPD6254	Approved
0.6837	Remote Similarity	NPD6256	Approved
0.6832	Remote Similarity	NPD6187	Approved
0.6832	Remote Similarity	NPD7451	Discontinued
0.6813	Remote Similarity	NPD3125	Approved
0.6811	Remote Similarity	NPD7695	Clinical (unspecified phase)
0.679	Remote Similarity	NPD4175	Approved
0.679	Remote Similarity	NPD4177	Approved
0.6786	Remote Similarity	NPD6253	Approved
0.677	Remote Similarity	NPD2585	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD8405	Clinical (unspecified phase)
0.6737	Remote Similarity	NPD6089	Clinical (unspecified phase)
0.6726	Remote Similarity	NPD5301	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD5725	Approved
0.6707	Remote Similarity	NPD6073	Approved
0.6707	Remote Similarity	NPD4497	Clinical (unspecified phase)
0.6704	Remote Similarity	NPD5967	Approved
0.6687	Remote Similarity	NPD4153	Approved
0.6687	Remote Similarity	NPD5323	Approved
0.6667	Remote Similarity	NPD9568	Approved
0.6667	Remote Similarity	NPD2209	Approved
0.6667	Remote Similarity	NPD7267	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7608	Discontinued
0.6667	Remote Similarity	NPD2211	Approved
0.6647	Remote Similarity	NPD2087	Approved
0.6647	Remote Similarity	NPD2088	Approved
0.6632	Remote Similarity	NPD6557	Phase 2
0.663	Remote Similarity	NPD8031	Discontinued
0.6629	Remote Similarity	NPD4186	Clinical (unspecified phase)
0.6628	Remote Similarity	NPD1967	Approved
0.6628	Remote Similarity	NPD1968	Approved
0.6625	Remote Similarity	NPD4706	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD3988	Approved
0.6609	Remote Similarity	NPD5614	Approved
0.6609	Remote Similarity	NPD7892	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD3987	Approved
0.6609	Remote Similarity	NPD5613	Approved
0.6596	Remote Similarity	NPD5445	Approved
0.6596	Remote Similarity	NPD6297	Approved
0.6587	Remote Similarity	NPD8416	Discontinued
0.6584	Remote Similarity	NPD2561	Approved
0.6584	Remote Similarity	NPD2562	Approved
0.6575	Remote Similarity	NPD4565	Clinical (unspecified phase)
0.6575	Remote Similarity	NPD4564	Clinical (unspecified phase)
0.6571	Remote Similarity	NPD6796	Discontinued
0.6568	Remote Similarity	NPD3553	Approved
0.6568	Remote Similarity	NPD3554	Approved
0.6568	Remote Similarity	NPD3552	Approved
0.6568	Remote Similarity	NPD3555	Approved
0.6566	Remote Similarity	NPD5299	Approved
0.6556	Remote Similarity	NPD4566	Approved
0.6556	Remote Similarity	NPD4567	Approved
0.6548	Remote Similarity	NPD3908	Approved
0.6548	Remote Similarity	NPD8643	Discontinued
0.6545	Remote Similarity	NPD6853	Approved
0.6545	Remote Similarity	NPD4125	Approved
0.6545	Remote Similarity	NPD6851	Approved
0.6536	Remote Similarity	NPD2541	Clinical (unspecified phase)
0.6528	Remote Similarity	NPD4157	Discontinued
0.6527	Remote Similarity	NPD5747	Discontinued
0.6527	Remote Similarity	NPD7634	Clinical (unspecified phase)
0.6526	Remote Similarity	NPD7132	Clinical (unspecified phase)
0.6524	Remote Similarity	NPD3588	Discontinued
0.6519	Remote Similarity	NPD856	Approved
0.6519	Remote Similarity	NPD16	Approved
0.6519	Remote Similarity	NPD317	Approved
0.6519	Remote Similarity	NPD318	Approved
0.6517	Remote Similarity	NPD6480	Clinical (unspecified phase)
0.6514	Remote Similarity	NPD6088	Approved
0.65	Remote Similarity	NPD7342	Discontinued
0.6497	Remote Similarity	NPD3659	Discontinued
0.6491	Remote Similarity	NPD6897	Clinical (unspecified phase)
0.6481	Remote Similarity	NPD2584	Suspended
0.6477	Remote Similarity	NPD2874	Phase 2
0.6471	Remote Similarity	NPD4126	Approved
0.6471	Remote Similarity	NPD4214	Discontinued
0.6468	Remote Similarity	NPD8162	Phase 2
0.6468	Remote Similarity	NPD8163	Clinical (unspecified phase)
0.6465	Remote Similarity	NPD7282	Approved
0.6463	Remote Similarity	NPD3055	Approved
0.6463	Remote Similarity	NPD3053	Approved
0.6457	Remote Similarity	NPD6884	Clinical (unspecified phase)
0.6453	Remote Similarity	NPD7720	Phase 2
0.6453	Remote Similarity	NPD2022	Approved
0.6443	Remote Similarity	NPD8025	Phase 2
0.6442	Remote Similarity	NPD4677	Discontinued
0.6438	Remote Similarity	NPD4504	Clinical (unspecified phase)
0.6437	Remote Similarity	NPD6676	Phase 2
0.6436	Remote Similarity	NPD5152	Clinical (unspecified phase)
0.6432	Remote Similarity	NPD3286	Discontinued
0.6429	Remote Similarity	NPD5165	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD2245	Discovery
0.6429	Remote Similarity	NPD7080	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD5745	Approved
0.6412	Remote Similarity	NPD2568	Approved
0.641	Remote Similarity	NPD6836	Approved
0.6409	Remote Similarity	NPD3589	Clinical (unspecified phase)
0.6406	Remote Similarity	NPD7280	Phase 3
0.6406	Remote Similarity	NPD7281	Phase 3
0.6402	Remote Similarity	NPD6325	Discontinued
0.6402	Remote Similarity	NPD5310	Approved
0.6402	Remote Similarity	NPD5311	Approved
0.64	Remote Similarity	NPD7602	Clinical (unspecified phase)
0.6392	Remote Similarity	NPD256	Approved
0.6392	Remote Similarity	NPD255	Approved
0.6391	Remote Similarity	NPD6346	Approved
0.6387	Remote Similarity	NPD5192	Clinical (unspecified phase)
0.6386	Remote Similarity	NPD9569	Approved
0.6384	Remote Similarity	NPD5556	Clinical (unspecified phase)
0.6384	Remote Similarity	NPD6419	Discontinued
0.6379	Remote Similarity	NPD2460	Phase 3
0.6379	Remote Similarity	NPD2459	Approved
0.6379	Remote Similarity	NPD2458	Approved
0.6378	Remote Similarity	NPD6767	Clinical (unspecified phase)
0.6375	Remote Similarity	NPD316	Approved
0.6373	Remote Similarity	NPD6556	Clinical (unspecified phase)
0.6369	Remote Similarity	NPD598	Approved
0.6369	Remote Similarity	NPD601	Approved
0.6369	Remote Similarity	NPD597	Approved
0.6369	Remote Similarity	NPD8315	Phase 1
0.6368	Remote Similarity	NPD5485	Approved
0.6368	Remote Similarity	NPD5484	Approved
0.6364	Remote Similarity	NPD3281	Clinical (unspecified phase)
0.6359	Remote Similarity	NPD6835	Approved
0.6354	Remote Similarity	NPD7193	Clinical (unspecified phase)
0.6352	Remote Similarity	NPD3123	Discovery
0.6348	Remote Similarity	NPD5229	Approved
0.6348	Remote Similarity	NPD5230	Approved
0.6343	Remote Similarity	NPD5481	Discontinued
0.6337	Remote Similarity	NPD4158	Clinical (unspecified phase)
0.6331	Remote Similarity	NPD259	Phase 1
0.6331	Remote Similarity	NPD1136	Approved
0.6331	Remote Similarity	NPD7086	Phase 2
0.6331	Remote Similarity	NPD1132	Approved

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