NPASS Compound

Natural Product: NPC526488

Natural Product ID	NPC526488
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ergocristam
IUPAC Name	(6~{a}~{R},9~{R})-~{N}-[(1~{S})-1-[(3~{S},8~{a}~{R})-3-benzyl-1,4-dioxo-6,7,8,8~{a}-tetrahydro-3~{H}-pyrrolo[1,2-a]pyrazine-2-carbonyl]-2-methyl-propyl]-7-methyl-6,6~{a},8,9-tetrahydro-4~{H}-indolo[4,3-fg]quinoline-9-carboxamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 83 89 0 0 0 0 0 0 0 0999 V2000 0.2328 2.6932 1.3490 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1830 2.0555 2.6312 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9473 1.8901 3.6079 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7666 0.6390 2.3904 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2682 -0.1178 1.7778 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0667 -1.0801 2.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7488 -1.2125 3.7105 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1557 -1.8373 1.8637 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2300 -0.8290 1.4890 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8187 -0.8148 0.3311 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8503 0.2067 0.0659 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9753 1.3453 0.8303 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9886 2.2011 0.4503 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8377 1.9387 -0.6375 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6983 0.7825 -1.4013 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6731 -0.0504 -0.9903 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6497 -1.1332 -1.8196 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6797 -0.9502 -2.7474 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3007 0.2259 -2.4670 N 0 0 0 0 0 0 0 0 0 0 0 0 4.6433 -2.1766 -1.5956 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4917 -1.7942 -0.7355 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7938 -2.9257 -0.2194 N 0 0 0 0 0 0 0 0 0 0 0 0 3.6553 -3.8454 0.4973 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6631 -2.5124 0.6146 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0625 0.7847 1.7618 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8139 1.6955 2.3203 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6370 0.1169 0.6584 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.9723 -1.0208 0.0601 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4798 -1.8799 0.8300 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8726 -1.1753 -1.4019 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0850 -2.5721 -1.8823 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6956 -2.3912 -3.2644 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9136 -0.9242 -3.4452 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9365 -0.4442 -2.0779 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.7537 0.5184 -1.4072 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2793 1.3693 -2.1675 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9169 0.4501 0.0584 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6312 1.6029 0.6720 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9350 1.9363 0.0353 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0499 1.1780 0.3774 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2772 1.4846 -0.1661 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3956 2.5372 -1.0432 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3027 3.3057 -1.3982 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0607 2.9827 -0.8373 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1256 3.7488 1.2520 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3450 2.7127 1.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1325 2.1637 0.4423 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9787 2.6672 3.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3613 2.8961 3.9111 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7668 1.2787 3.1637 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6253 1.4054 4.5325 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8690 0.2533 3.4547 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4930 0.0047 0.7658 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5537 -2.5819 2.5569 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4997 -0.1039 2.2480 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3378 1.5635 1.6594 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1477 3.1061 0.9953 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6267 2.6212 -0.9203 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9343 -1.6279 -3.5461 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0975 0.6344 -2.9745 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2937 -2.5141 -2.6131 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1450 -3.0748 -1.1627 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7560 -1.2518 -1.4040 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5843 -3.3430 0.8448 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9620 -4.6337 -0.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1575 -4.2914 1.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0621 -1.8223 -0.0066 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0677 -3.4069 0.8204 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8724 -0.8373 -1.7620 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8244 -3.0817 -1.2074 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1486 -3.1569 -1.9193 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0570 -2.8061 -4.0590 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6958 -2.8867 -3.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0549 -0.4427 -3.9912 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8284 -0.6613 -4.0013 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5893 -0.4683 0.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0244 2.5186 0.6603 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9025 1.3686 1.7374 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9996 0.3450 1.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1645 0.9229 0.0721 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3396 2.8098 -1.4909 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3516 4.1361 -2.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2068 3.5831 -1.0862 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 24 1 0 4 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 40 41 1 0 41 42 2 0 42 43 1 0 43 44 2 0 24 8 1 0 37 27 1 0 44 39 1 0 21 10 1 0 34 30 1 0 16 11 1 0 19 15 1 0 1 45 1 0 1 46 1 0 1 47 1 0 2 48 1 0 3 49 1 0 3 50 1 0 3 51 1 0 4 52 1 1 5 53 1 0 8 54 1 1 9 55 1 0 12 56 1 0 13 57 1 0 14 58 1 0 18 59 1 0 19 60 1 0 20 61 1 0 20 62 1 0 21 63 1 6 23 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 24 68 1 0 30 69 1 6 31 70 1 0 31 71 1 0 32 72 1 0 32 73 1 0 33 74 1 0 33 75 1 0 37 76 1 6 38 77 1 0 38 78 1 0 40 79 1 0 41 80 1 0 42 81 1 0 43 82 1 0 44 83 1 0 M END

Standard InCHIKey	KMDKLWZQLMBIBS-HVWSGMRBSA-N
Standard InCHI	InChI=1S/C35H39N5O4/c1-20(2)31(35(44)40-29(15-21-9-5-4-6-10-21)33(42)39-14-8-13-27(39)34(40)43)37-32(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-28(25)38(3)19-23/h4-7,9-12,16,18,20,23,27-29,31,36H,8,13-15,17,19H2,1-3H3,(H,37,41)/t23-,27-,28-,29+,31+/m1/s1
SMILES	CC(C)[C@H](NC(=O)[C@@H]1C=C2C3=CC=CC4=C3C(=CN4)C[C@H]2N(C)C1)C(=O)N1C(=O)[C@H]2CCCN2C(=O)[C@@H]1CC1=CC=CC=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	593.3	Volume:	612.528 ? Van der Waals volume.
Dense:	0.969	LogP:	2.861 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.831 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.778 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	39.0
TPSA:	105.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	7.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.457	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.408	Fsp³:	0.429
MCE-18:	134.4 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.826	Fluc inhibitor:	0.015 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.958 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.962 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.963

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.76	MDCK Permeability:	-5.028
Pgp-inhibitor:	1.0	Pgp-substrate:	0.47
PAMPA:	0.001 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.39
20% Bioavailability (F20%):	0.894	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.012
Plasma Protein Binding (PPB):	93.111%	Volume Distribution (VD):	-0.044
Fu:	5.94% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.569
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.671	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.973	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.016	CYP2D6-substrate:	0.558
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.027 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

10.886

Half-life (T1/2):

1.367

ADMET: Toxicity

hERG Blockers:	0.431	hERG Blockers (10um):	0.468
Human Hepatotoxicity (H-HT):	0.674	Drug-induced Liver Injury (DILI):	0.446
AMES Toxicity:	0.481	Rat Oral Acute Toxicity:	0.792
Maximum Recommended Daily Dose:	0.979	Skin Sensitization:	0.467
Carcinogencity:	0.435	Eye Corrosion:	0.0
Eye Irritation:	0.016	Respiratory Toxicity:	0.917
Drug-induced Neurotoxicity:	0.985	Ototoxicity:	0.783
Hematotoxicity:	0.304	Drug-induced Nephrotoxicity:	0.608
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.193	Hek293 Cytotoxicity:	0.748
BCF:	1.631 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.25 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.794 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.315 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO43884	Claviceps grohii	Species	Clavicipitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	Organism Name	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

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC526488 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	28537
0.1-0.2	20162
0.2-0.3	1084
0.3-0.4	64
0.4-0.5	1
0.5-0.6	6
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6484	Remote Similarity	NPC611966
0.6296	Remote Similarity	NPC56109
0.6296	Remote Similarity	NPC191382
0.6264	Remote Similarity	NPC604662
0.5741	Remote Similarity	NPC603739
0.5268	Remote Similarity	NPC155444
0.5155	Remote Similarity	NPC68354
0.5114	Remote Similarity	NPC606264
0.5111	Remote Similarity	NPC275305
0.5111	Remote Similarity	NPC37423

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC526488 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3645
0.1-0.2	5284
0.2-0.3	186
0.3-0.4	17
0.4-0.5	13
0.5-0.6	4
0.6-0.7	1
0.7-0.8	0
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
0.6296	Remote Similarity	NPD7781	Phase 4
0.5913	Remote Similarity	NPD7780	Approved
0.5495	Remote Similarity	NPD4075	Phase 2
0.5204	Remote Similarity	NPD4079	Phase 4
0.5155	Remote Similarity	NPD3506	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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